{"entity": "label", "iuid": "68b5b7fa49534576bad740f9cbd9b12b", "timestamp": "2026-07-14T00:52:04.171Z", "links": {"self": {"href": "https://publications.scilifelab.se/label/Karolinska%20High%20Throughput%20Center%20%28KHTC%29.json"}, "display": {"href": "https://publications.scilifelab.se/label/Karolinska%20High%20Throughput%20Center%20%28KHTC%29"}}, "value": "Karolinska High Throughput Center (KHTC)", "started": "2013", "ended": "2016", "created": "2017-05-02T12:10:00.542Z", "modified": "2021-03-15T14:20:38.039Z", "accounts": [{"entity": "account", "iuid": "32a436398938412b93e7ddcef018c708", "timestamp": "2026-07-14T00:52:04.171Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/christopher.erdmann%40scilifelab.uu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/christopher.erdmann%40scilifelab.uu.se"}}, "email": "christopher.erdmann@scilifelab.uu.se", "name": "Christopher Erdmann", "orcid": "", "role": "curator", "status": "enabled", "login": "2024-08-16T11:56:57.787Z", "created": "2024-08-16T10:01:32.844Z", "modified": "2025-10-17T13:05:06.782Z"}, {"entity": "account", "iuid": "6a38350bd21f4fb6aeeb1530037a99ae", "timestamp": "2026-07-14T00:52:04.171Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/sune.joubert%40scilifelab.uu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/sune.joubert%40scilifelab.uu.se"}}, "email": "sune.joubert@scilifelab.uu.se", "name": "Sun\u00e9 Joubert", "orcid": "", "role": "curator", "status": "enabled", "login": "2025-10-31T11:15:37.113Z", "created": "2024-08-16T10:01:02.800Z", "modified": "2025-10-31T11:15:37.113Z"}, {"entity": "account", "iuid": "9b40d77f45744ac1a914a25559d6430b", "timestamp": "2026-07-14T00:52:04.171Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/jianping.liu%40ki.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/jianping.liu%40ki.se"}}, "email": "jianping.liu@ki.se", "name": "Jianping Liu", "orcid": null, "role": "curator", "status": "enabled", "login": null, "created": "2017-05-03T12:52:06.038Z", "modified": "2017-09-18T14:34:32.467Z"}, {"entity": "account", "iuid": "aff42d77889846999ae8da088684c9af", "timestamp": "2026-07-14T00:52:04.171Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/anders.eriksson%40ki.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/anders.eriksson%40ki.se"}}, "email": "anders.eriksson@ki.se", "name": "Anders Eriksson", "orcid": null, "role": "curator", "status": "enabled", "login": null, "created": "2017-05-02T12:10:05.264Z", "modified": "2017-09-18T14:37:01.904Z"}], "publications_count": 28, "publications": [{"entity": "publication", "iuid": "c4b1469d0e5a45dab36159947e7afc42", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c4b1469d0e5a45dab36159947e7afc42.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c4b1469d0e5a45dab36159947e7afc42"}}, "title": "Multifunctional Hyaluronic Acid and Chondroitin Sulfate Nanoparticles: Impact of Glycosaminoglycan Presentation on Receptor Mediated Cellular Uptake and Immune Activation.", "authors": [{"family": "Oommen", "given": "Oommen P", "initials": "OP"}, {"family": "Duehrkop", "given": "Claudia", "initials": "C"}, {"family": "Nilsson", "given": "Bo", "initials": "B"}, {"family": "Hilborn", "given": "J\u00f6ns", "initials": "J"}, {"family": "Varghese", "given": "Oommen P", "initials": "OP"}], "type": "journal article", "published": "2016-08-17", "journal": {"volume": "8", "issn": "1944-8252", "issue": "32", "pages": "20614-20624", "title": "ACS Appl Mater Interfaces", "issn-l": "1944-8244"}, "abstract": "Hyaluronic acid (HA) and chondroitin sulfate (CS) polymers are extensively used for various biomedical applications, such as for tissue engineering, drug delivery, and gene delivery. Although both these biopolymers are known to target cell surface CD44 receptors, their relative cellular targeting properties and immune activation potential have never been evaluated. In this article, we present the synthesis and characterization of novel self-assembled supramolecular HA and CS nanoparticles (NPs). These NPs were developed using fluorescein as a hydrophobic component that induced amphiphilicity in biopolymers and also efficiently stabilized anticancer drug doxorubicin (DOX) promoting a near zero-order drug release. The cellular uptake and cytotoxicity studies of these NPs in different human cancer lines, namely, human colorectal carcinoma cell line HCT116 and human breast cancer cell line MCF-7 demonstrated dose dependent cytotoxicity. Interestingly, both NPs showed CD44 dependent cellular uptake with the CS-DOX NP displaying higher dose-dependent cytotoxicity than the HA-DOX NP in different mammalian cells tested. Immunological evaluation of these nanocarriers in an ex vivo human whole blood model revealed that unlike unmodified polymers, the HA NP and CS NP surprisingly showed platelet aggregation and thrombin-antithrombin complex formation at high concentrations (0.8 mg/mL). We also observed a clear difference in early- and late-stage complement activation (C3a and sC5b-9) with CS and CS NP triggering significant complement activation at high concentrations (0.08-0.8 mg/mL), unlike HA and HA NP. These results offer new insight into designing glycosaminoglycan-based NPs and understanding their hematological responses and targeting ability.", "doi": "10.1021/acsami.6b06823", "pmid": "27468113", "labels": {"Karolinska High Throughput Center (KHTC)": "Service"}, "xrefs": [], "notes": [], "created": "2017-05-10T14:29:00.543Z", "modified": "2017-06-12T11:37:46.468Z"}, {"entity": "publication", "iuid": "cb8edafe31694c5892cd5fbd033c2ec1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cb8edafe31694c5892cd5fbd033c2ec1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cb8edafe31694c5892cd5fbd033c2ec1"}}, "title": "Chondroitin sulfate derived theranostic nanoparticles for targeted drug delivery.", "authors": [{"family": "Varghese", "given": "Oommen P", "initials": "OP"}, {"family": "Liu", "given": "Jianping", "initials": "J"}, {"family": "Sundaram", "given": "Karthi", "initials": "K"}, {"family": "Hilborn", "given": "J\u00f6ns", "initials": "J"}, {"family": "Oommen", "given": "Oommen P", "initials": "OP"}], "type": "journal article", "published": "2016-08-16", "journal": {"volume": "4", "issn": "2047-4849", "issue": "9", "pages": "1310-1313", "title": "Biomater Sci", "issn-l": "2047-4830"}, "abstract": "Glycosaminoglycan derived nanoparticles are a promising delivery system owing to their unique tumour targeting ability. Exploiting fluorescein for inducing amphiphilicity in these biopolymers provides inherent imaging and drug stabilization capabilities by \u03c0-\u03c0 stacking interactions with aromatic antineoplastic agents. This offers a versatile and highly customizable nanocarrier with narrow size distribution and high drug loading efficiency (80%) with sustained drug release.", "doi": "10.1039/c6bm00335d", "pmid": "27431007", "labels": {"Karolinska High Throughput Center (KHTC)": "Service"}, "xrefs": [], "notes": [], "created": "2017-05-03T12:59:36.412Z", "modified": "2017-06-12T11:37:46.964Z"}, {"entity": "publication", "iuid": "9dbdcd74f6ad456e982606a5bcc4e5df", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9dbdcd74f6ad456e982606a5bcc4e5df.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9dbdcd74f6ad456e982606a5bcc4e5df"}}, "title": "Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications.", "authors": [{"family": "Ch'ng", "given": "Jun-Hong", "initials": "JH"}, {"family": "Moll", "given": "Kirsten", "initials": "K"}, {"family": "Quintana", "given": "Maria Del Pilar", "initials": "Mdel P"}, {"family": "Chan", "given": "Sherwin Chun Leung", "initials": "SC"}, {"family": "Masters", "given": "Ellen", "initials": "E"}, {"family": "Moles", "given": "Ernest", "initials": "E"}, {"family": "Liu", "given": "Jianping", "initials": "J"}, {"family": "Eriksson", "given": "Anders B", "initials": "AB"}, {"family": "Wahlgren", "given": "Mats", "initials": "M"}], "type": "journal article", "published": "2016-07-11", "journal": {"volume": "6", "issn": "2045-2322", "issue": null, "pages": "29317", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "The spread of artemisinin-resistant parasites could lead to higher incidence of patients with malaria complications. However, there are no current treatments that directly dislodge sequestered parasites from the microvasculature. We show that four common antiplasmodial drugs do not disperse rosettes (erythrocyte clusters formed by malaria parasites) and therefore develop a cell-based high-throughput assay to identify potential rosette-disrupting compounds. A pilot screen of 2693 compounds identified Malaria Box compound MMV006764 as a potential candidate. Although it reduced rosetting by a modest 20%, MMV006764 was validated to be similarly effective against both blood group O and A rosettes of three laboratory parasite lines. Coupled with its antiplasmodial activity and drug-likeness, MMV006764 represents the first small-molecule compound that disrupts rosetting and could potentially be used in a resource-limited setting to treat patients deteriorating rapidly from malaria complications. Such dual-action drugs that simultaneously restore microcirculation and reduce parasite load could significantly reduce malaria morbidity and mortality.", "doi": "10.1038/srep29317", "pmid": "27403804", "labels": {"Karolinska High Throughput Center (KHTC)": "Service"}, "xrefs": [{"db": "pii", "key": "srep29317"}, {"db": "pmc", "key": "PMC4941523"}], "notes": [], "created": "2017-05-08T07:56:47.273Z", "modified": "2017-06-12T11:37:46.608Z"}, {"entity": "publication", "iuid": "77da5ef1c8c94bc48cce4fe25d028fe4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/77da5ef1c8c94bc48cce4fe25d028fe4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/77da5ef1c8c94bc48cce4fe25d028fe4"}}, "title": "Chondroitin sulfate coated gold nanoparticles: a new strategy to resolve multidrug resistance and thromboinflammation.", "authors": [{"family": "Gurav", "given": "Deepanjali", "initials": "D"}, {"family": "Varghese", "given": "Oommen P", "initials": "OP"}, {"family": "Hamad", "given": "Osama A", "initials": "OA"}, {"family": "Nilsson", "given": "Bo", "initials": "B"}, {"family": "Hilborn", "given": "J\u00f6ns", "initials": "J"}, {"family": "Oommen", "given": "Oommen P", "initials": "OP"}], "type": "journal article", "published": "2016-01-18", "journal": {"volume": "52", "issn": "1364-548X", "issue": "5", "pages": "966-969", "title": "Chem. Commun. (Camb.)", "issn-l": "1359-7345"}, "abstract": "We have developed the first chondroitin sulfate polymer coated gold nanoparticles that can simultaneously overcome mulidrug resistance in cancer cells and suppress thromboinflammation triggered by the chemotherapeutic drug.", "doi": "10.1039/c5cc09215a", "pmid": "26587574", "labels": {"Karolinska High Throughput Center (KHTC)": "Service"}, "xrefs": [], "notes": [], "created": "2017-05-03T12:59:36.116Z", "modified": "2017-06-12T11:37:46.784Z"}, {"entity": "publication", "iuid": "eddaaa22ebbe4684be096bfc736855bd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/eddaaa22ebbe4684be096bfc736855bd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/eddaaa22ebbe4684be096bfc736855bd"}}, "title": "Structural insights into the DNA-binding specificity of E2F family transcription factors.", "authors": [{"family": "Morgunova", "given": "Ekaterina", "initials": "E"}, {"family": "Yin", "given": "Yimeng", "initials": "Y"}, {"family": "Jolma", "given": "Arttu", "initials": "A"}, {"family": "Dave", "given": "Kashyap", "initials": "K"}, {"family": "Schmierer", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-9082-7022", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3ee96f9eb454850be6db3318b28479f.json"}}, {"family": "Popov", "given": "Alexander", "initials": "A"}, {"family": "Eremina", "given": "Nadejda", "initials": "N"}, {"family": "Nilsson", "given": "Lennart", "initials": "L"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}], "type": "journal article", "published": "2015-12-03", "journal": {"volume": "6", "issn": "2041-1723", "issue": "1", "pages": "10050", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "The mammalian cell cycle is controlled by the E2F family of transcription factors. Typical E2Fs bind to DNA as heterodimers with the related dimerization partner (DP) proteins, whereas the atypical E2Fs, E2F7 and E2F8 contain two DNA-binding domains (DBDs) and act as repressors. To understand the mechanism of repression, we have resolved the structure of E2F8 in complex with DNA at atomic resolution. We find that the first and second DBDs of E2F8 resemble the DBDs of typical E2F and DP proteins, respectively. Using molecular dynamics simulations, biochemical affinity measurements and chromatin immunoprecipitation, we further show that both atypical and typical E2Fs bind to similar DNA sequences in vitro and in vivo. Our results represent the first crystal structure of an E2F protein with two DBDs, and reveal the mechanism by which atypical E2Fs can repress canonical E2F target genes and exert their negative influence on cell cycle progression.", "doi": "10.1038/ncomms10050", "pmid": "26632596", "labels": {"Protein Science Facility (PSF)": null, "Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "ncomms10050"}, {"db": "pmc", "key": "PMC4686757"}, {"db": "BioProject", "key": "PRJEB8671"}, {"db": "PDB", "key": "4YO2"}], "notes": [], "created": "2017-05-02T12:56:56.387Z", "modified": "2021-07-06T14:42:14.622Z"}, {"entity": "publication", "iuid": "d5d5bbb4d07a433581e6d642f7c005d0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d5d5bbb4d07a433581e6d642f7c005d0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d5d5bbb4d07a433581e6d642f7c005d0"}}, "title": "DNA-dependent formation of transcription factor pairs alters their binding specificity.", "authors": [{"family": "Jolma", "given": "Arttu", "initials": "A"}, {"family": "Yin", "given": "Yimeng", "initials": "Y"}, {"family": "Nitta", "given": "Kazuhiro R", "initials": "KR"}, {"family": "Dave", "given": "Kashyap", "initials": "K"}, {"family": "Popov", "given": "Alexander", "initials": "A"}, {"family": "Taipale", "given": "Minna", "initials": "M"}, {"family": "Enge", "given": "Martin", "initials": "M"}, {"family": "Kivioja", "given": "Teemu", "initials": "T"}, {"family": "Morgunova", "given": "Ekaterina", "initials": "E"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}], "type": "journal article", "published": "2015-11-19", "journal": {"volume": "527", "issn": "1476-4687", "issue": "7578", "pages": "384-388", "title": "Nature", "issn-l": "0028-0836"}, "abstract": "Gene expression is regulated by transcription factors (TFs), proteins that recognize short DNA sequence motifs. Such sequences are very common in the human genome, and an important determinant of the specificity of gene expression is the cooperative binding of multiple TFs to closely located motifs. However, interactions between DNA-bound TFs have not been systematically characterized. To identify TF pairs that bind cooperatively to DNA, and to characterize their spacing and orientation preferences, we have performed consecutive affinity-purification systematic evolution of ligands by exponential enrichment (CAP-SELEX) analysis of 9,400 TF-TF-DNA interactions. This analysis revealed 315 TF-TF interactions recognizing 618 heterodimeric motifs, most of which have not been previously described. The observed cooperativity occurred promiscuously between TFs from diverse structural families. Structural analysis of the TF pairs, including a novel crystal structure of MEIS1 and DLX3 bound to their identified recognition site, revealed that the interactions between the TFs were predominantly mediated by DNA. Most TF pair sites identified involved a large overlap between individual TF recognition motifs, and resulted in recognition of composite sites that were markedly different from the individual TF's motifs. Together, our results indicate that the DNA molecule commonly plays an active role in cooperative interactions that define the gene regulatory lexicon.", "doi": "10.1038/nature15518", "pmid": "26550823", "labels": {"Protein Science Facility (PSF)": null, "Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "nature15518"}, {"db": "BioProject", "key": "PRJEB7934"}, {"db": "PDB", "key": "4XRM"}, {"db": "PDB", "key": "4XRS"}, {"db": "PDB", "key": "5BNG"}], "notes": [], "created": "2017-05-02T12:56:32.252Z", "modified": "2017-09-06T11:42:09.394Z"}, {"entity": "publication", "iuid": "828f27fe39364a6aae1cd83b61b33783", "links": {"self": {"href": "https://publications.scilifelab.se/publication/828f27fe39364a6aae1cd83b61b33783.json"}, "display": {"href": "https://publications.scilifelab.se/publication/828f27fe39364a6aae1cd83b61b33783"}}, "title": "CTCF/cohesin-binding sites are frequently mutated in cancer.", "authors": [{"family": "Katainen", "given": "Riku", "initials": "R"}, {"family": "Dave", "given": "Kashyap", "initials": "K"}, {"family": "Pitk\u00e4nen", "given": "Esa", "initials": "E"}, {"family": "Palin", "given": "Kimmo", "initials": "K"}, {"family": "Kivioja", "given": "Teemu", "initials": "T"}, {"family": "V\u00e4lim\u00e4ki", "given": "Niko", "initials": "N"}, {"family": "Gylfe", "given": "Alexandra E", "initials": "AE"}, {"family": "Ristolainen", "given": "Heikki", "initials": "H"}, {"family": "H\u00e4nninen", "given": "Ulrika A", "initials": "UA"}, {"family": "Cajuso", "given": "Tatiana", "initials": "T"}, {"family": "Kondelin", "given": "Johanna", "initials": "J"}, {"family": "Tanskanen", "given": "Tomas", "initials": "T"}, {"family": "Mecklin", "given": "Jukka-Pekka", "initials": "JP"}, {"family": "J\u00e4rvinen", "given": "Heikki", "initials": "H"}, {"family": "Renkonen-Sinisalo", "given": "Laura", "initials": "L"}, {"family": "Lepist\u00f6", "given": "Anna", "initials": "A"}, {"family": "Kaasinen", "given": "Eevi", "initials": "E"}, {"family": "Kilpivaara", "given": "Outi", "initials": "O"}, {"family": "Tuupanen", "given": "Sari", "initials": "S"}, {"family": "Enge", "given": "Martin", "initials": "M"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}, {"family": "Aaltonen", "given": "Lauri A", "initials": "LA"}], "type": "journal article", "published": "2015-07-00", "journal": {"volume": "47", "issn": "1546-1718", "issue": "7", "pages": "818-821", "title": "Nat. Genet.", "issn-l": "1061-4036"}, "abstract": "Cohesin is present in almost all active enhancer regions, where it is associated with transcription factors. Cohesin frequently colocalizes with CTCF (CCCTC-binding factor), affecting genomic stability, expression and epigenetic homeostasis. Cohesin subunits are mutated in cancer, but CTCF/cohesin-binding sites (CBSs) in DNA have not been examined for mutations. Here we report frequent mutations at CBSs in cancers displaying a mutational signature where mutations in A\u2022T base pairs predominate. Integration of whole-genome sequencing data from 213 colorectal cancer (CRC) samples and chromatin immunoprecipitation sequencing (ChIP-exo) data identified frequent point mutations at CBSs. In contrast, CRCs showing an ultramutator phenotype caused by defects in the exonuclease domain of DNA polymerase \u025b (POLE) displayed significantly fewer mutations at and adjacent to CBSs. Analysis of public data showed that multiple cancer types accumulate CBS mutations. CBSs are a major mutational hotspot in the noncoding cancer genome.", "doi": "10.1038/ng.3335", "pmid": "26053496", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "ng.3335"}], "notes": [], "created": "2017-05-02T12:58:24.092Z", "modified": "2017-05-30T13:18:28.491Z"}, {"entity": "publication", "iuid": "b518c7e8ae3e47fea2d5749ddffd5f41", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b518c7e8ae3e47fea2d5749ddffd5f41.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b518c7e8ae3e47fea2d5749ddffd5f41"}}, "title": "Conservation of transcription factor binding specificities across 600 million years of bilateria evolution.", "authors": [{"family": "Nitta", "given": "Kazuhiro R", "initials": "KR"}, {"family": "Jolma", "given": "Arttu", "initials": "A"}, {"family": "Yin", "given": "Yimeng", "initials": "Y"}, {"family": "Morgunova", "given": "Ekaterina", "initials": "E"}, {"family": "Kivioja", "given": "Teemu", "initials": "T"}, {"family": "Akhtar", "given": "Junaid", "initials": "J"}, {"family": "Hens", "given": "Korneel", "initials": "K"}, {"family": "Toivonen", "given": "Jarkko", "initials": "J"}, {"family": "Deplancke", "given": "Bart", "initials": "B"}, {"family": "Furlong", "given": "Eileen E M", "initials": "EE"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}], "type": "journal article", "published": "2015-03-17", "journal": {"volume": "4", "issn": "2050-084X", "issue": null, "title": "Elife", "issn-l": "2050-084X"}, "abstract": "Divergent morphology of species has largely been ascribed to genetic differences in the tissue-specific expression of proteins, which could be achieved by divergence in cis-regulatory elements or by altering the binding specificity of transcription factors (TFs). The relative importance of the latter has been difficult to assess, as previous systematic analyses of TF binding specificity have been performed using different methods in different species. To address this, we determined the binding specificities of 242 Drosophila TFs, and compared them to human and mouse data. This analysis revealed that TF binding specificities are highly conserved between Drosophila and mammals, and that for orthologous TFs, the similarity extends even to the level of very subtle dinucleotide binding preferences. The few human TFs with divergent specificities function in cell types not found in fruit flies, suggesting that evolution of TF specificities contributes to emergence of novel types of differentiated cells.", "doi": "10.7554/eLife.04837", "pmid": "25779349", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pmc", "key": "PMC4362205"}], "notes": [], "created": "2017-05-02T12:57:36.362Z", "modified": "2017-05-30T15:06:14.513Z"}, {"entity": "publication", "iuid": "7a88ee7a5e464f3eb6f00e07ace967f5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7a88ee7a5e464f3eb6f00e07ace967f5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7a88ee7a5e464f3eb6f00e07ace967f5"}}, "title": "Identification of 33 candidate oncogenes by screening for base-specific mutations.", "authors": [{"family": "Tuupanen", "given": "S", "initials": "S"}, {"family": "H\u00e4nninen", "given": "U A", "initials": "UA"}, {"family": "Kondelin", "given": "J", "initials": "J"}, {"family": "von Nandelstadh", "given": "P", "initials": "P"}, {"family": "Cajuso", "given": "T", "initials": "T"}, {"family": "Gylfe", "given": "A E", "initials": "AE"}, {"family": "Katainen", "given": "R", "initials": "R"}, {"family": "Tanskanen", "given": "T", "initials": "T"}, {"family": "Ristolainen", "given": "H", "initials": "H"}, {"family": "B\u00f6hm", "given": "J", "initials": "J"}, {"family": "Mecklin", "given": "J-P", "initials": "JP"}, {"family": "J\u00e4rvinen", "given": "H", "initials": "H"}, {"family": "Renkonen-Sinisalo", "given": "L", "initials": "L"}, {"family": "Andersen", "given": "C L", "initials": "CL"}, {"family": "Taipale", "given": "M", "initials": "M"}, {"family": "Taipale", "given": "J", "initials": "J"}, {"family": "Vahteristo", "given": "P", "initials": "P"}, {"family": "Lehti", "given": "K", "initials": "K"}, {"family": "Pitk\u00e4nen", "given": "E", "initials": "E"}, {"family": "Aaltonen", "given": "L A", "initials": "LA"}], "type": "journal article", "published": "2014-10-14", "journal": {"volume": "111", "issn": "1532-1827", "issue": "8", "pages": "1657-1662", "title": "Br. J. Cancer", "issn-l": "0007-0920"}, "abstract": "Genes with recurrent codon-specific somatic mutations are likely drivers of tumorigenesis and potential therapeutic targets. Hypermutable cancers may represent a sensitive system for generation and selection of oncogenic mutations.\n\nWe utilised exome-sequencing data on 25 sporadic microsatellite-instable (MSI) colorectal cancers (CRCs) and searched for base-specific somatic mutation hotspots.\n\nWe identified novel mutation hotspots in 33 genes. Fourteen genes displayed mutations in the validation set of 254 MSI CRCs: ANTXR1, MORC2, CEP135, CRYBB1, GALNT9, KRT82, PI15, SLC36A1, CNTF, GLDC, MBTPS1, OR9Q2, R3HDM1 and TTPAL. A database search found examples of the hotspot mutations in multiple cancer types.\n\nThis work reveals a variety of new recurrent candidate oncogene mutations to be further scrutinised as potential therapeutic targets.", "doi": "10.1038/bjc.2014.429", "pmid": "25117815", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "bjc2014429"}, {"db": "pmc", "key": "PMC4200084"}], "notes": [], "created": "2017-05-04T14:57:07.198Z", "modified": "2017-05-30T11:44:25.587Z"}, {"entity": "publication", "iuid": "c395acd664b54724903e9e5bea473551", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c395acd664b54724903e9e5bea473551.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c395acd664b54724903e9e5bea473551"}}, "title": "HemR is an OmpR/PhoB-like response regulator from Leptospira, which simultaneously effects transcriptional activation and repression of key haem metabolism genes.", "authors": [{"family": "Morero", "given": "Natalia R", "initials": "NR"}, {"family": "Botti", "given": "Horacio", "initials": "H"}, {"family": "Nitta", "given": "Kazuhiro R", "initials": "KR"}, {"family": "Carri\u00f3n", "given": "Federico", "initials": "F"}, {"family": "Obal", "given": "Gonzalo", "initials": "G"}, {"family": "Picardeau", "given": "Mathieu", "initials": "M"}, {"family": "Buschiazzo", "given": "Alejandro", "initials": "A"}], "type": "journal article", "published": "2014-10-00", "journal": {"volume": "94", "issn": "1365-2958", "issue": "2", "pages": "340-352", "title": "Mol. Microbiol.", "issn-l": "0950-382X"}, "abstract": "Several Leptospira species cause leptospirosis, the most extended zoonosis worldwide. In bacteria, two-component systems constitute key signalling pathways, some of which are involved in pathogenesis. The physiological roles of two-component systems in Leptospira are largely unknown, despite identifying several dozens within their genomes. Biochemical confirmation of an operative phosphorelaying two-component system has been obtained so far only for the Hklep/Rrlep pair. It is known that hklep/rrlep knockout strains of Leptospira biflexa result in haem auxotrophy, although their de novo biosynthesis machinery remains fully functional. Haem is essential for Leptospira, but information about Hklep/Rrlep effector function(s) and target(s) is still lacking. We are now reporting a thorough molecular characterization of this system, which we rename HemK/HemR. The DNA HemR-binding motif was determined, and found within the genomes of saprophyte and pathogenic Leptospira. In this way, putative HemR-regulated genes were pinpointed, including haem catabolism-related (hmuO - haem oxygenase) and biosynthesis-related (the hemA/C/D/B/L/E/N/G operon). Specific HemR binding to these two promoters was quantified, and a dual function was observed in vivo, inversely repressing the hmuO, while activating the hemA operon transcription. The crystal structure of HemR receiver domain was determined, leading to a mechanistic model for its dual regulatory role.", "doi": "10.1111/mmi.12763", "pmid": "25145397", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:57:07.805Z", "modified": "2017-05-30T11:44:32.833Z"}, {"entity": "publication", "iuid": "04969cb9430a410798ba87f6a197d420", "links": {"self": {"href": "https://publications.scilifelab.se/publication/04969cb9430a410798ba87f6a197d420.json"}, "display": {"href": "https://publications.scilifelab.se/publication/04969cb9430a410798ba87f6a197d420"}}, "title": "The Glanville fritillary genome retains an ancient karyotype and reveals selective chromosomal fusions in Lepidoptera.", "authors": [{"family": "Ahola", "given": "Virpi", "initials": "V"}, {"family": "Lehtonen", "given": "Rainer", "initials": "R"}, {"family": "Somervuo", "given": "Panu", "initials": "P"}, {"family": "Salmela", "given": "Leena", "initials": "L"}, {"family": "Koskinen", "given": "Patrik", "initials": "P"}, {"family": "Rastas", "given": "Pasi", "initials": "P"}, {"family": "V\u00e4lim\u00e4ki", "given": "Niko", "initials": "N"}, {"family": "Paulin", "given": "Lars", "initials": "L"}, {"family": "Kvist", "given": "Jouni", "initials": "J"}, {"family": "Wahlberg", "given": "Niklas", "initials": "N"}, {"family": "Tanskanen", "given": "Jaakko", "initials": "J"}, {"family": "Hornett", "given": "Emily A", "initials": "EA"}, {"family": "Ferguson", "given": "Laura C", "initials": "LC"}, {"family": "Luo", "given": "Shiqi", "initials": "S"}, {"family": "Cao", "given": "Zijuan", "initials": "Z"}, {"family": "de Jong", "given": "Maaike A", "initials": "MA"}, {"family": "Duplouy", "given": "Anne", "initials": "A"}, {"family": "Smolander", "given": "Olli-Pekka", "initials": "OP"}, {"family": "Vogel", "given": "Heiko", "initials": "H"}, {"family": "McCoy", "given": "Rajiv C", "initials": "RC"}, {"family": "Qian", "given": "Kui", "initials": "K"}, {"family": "Chong", "given": "Wong Swee", "initials": "WS"}, {"family": "Zhang", "given": "Qin", "initials": "Q"}, {"family": "Ahmad", "given": "Freed", "initials": "F"}, {"family": "Haukka", "given": "Jani K", "initials": "JK"}, {"family": "Joshi", "given": "Aruj", "initials": "A"}, {"family": "Saloj\u00e4rvi", "given": "Jarkko", "initials": "J"}, {"family": "Wheat", "given": "Christopher W", "initials": "CW"}, {"family": "Grosse-Wilde", "given": "Ewald", "initials": "E"}, {"family": "Hughes", "given": "Daniel", "initials": "D"}, {"family": "Katainen", "given": "Riku", "initials": "R"}, {"family": "Pitk\u00e4nen", "given": "Esa", "initials": "E"}, {"family": "Ylinen", "given": "Johannes", "initials": "J"}, {"family": "Waterhouse", "given": "Robert M", "initials": "RM"}, {"family": "Turunen", "given": "Mikko", "initials": "M"}, {"family": "V\u00e4h\u00e4rautio", "given": "Anna", "initials": "A"}, {"family": "Ojanen", "given": "Sami P", "initials": "SP"}, {"family": "Schulman", "given": "Alan H", "initials": "AH"}, {"family": "Taipale", "given": "Minna", "initials": "M"}, {"family": "Lawson", "given": "Daniel", "initials": "D"}, {"family": "Ukkonen", "given": "Esko", "initials": "E"}, {"family": "M\u00e4kinen", "given": "Veli", "initials": "V"}, {"family": "Goldsmith", "given": "Marian R", "initials": "MR"}, {"family": "Holm", "given": "Liisa", "initials": "L"}, {"family": "Auvinen", "given": "Petri", "initials": "P"}, {"family": "Frilander", "given": "Mikko J", "initials": "MJ"}, {"family": "Hanski", "given": "Ilkka", "initials": "I"}], "type": "journal article", "published": "2014-09-05", "journal": {"volume": "5", "issn": "2041-1723", "issue": null, "pages": "4737", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Previous studies have reported that chromosome synteny in Lepidoptera has been well conserved, yet the number of haploid chromosomes varies widely from 5 to 223. Here we report the genome (393\u2009Mb) of the Glanville fritillary butterfly (Melitaea cinxia; Nymphalidae), a widely recognized model species in metapopulation biology and eco-evolutionary research, which has the putative ancestral karyotype of n=31. Using a phylogenetic analyses of Nymphalidae and of other Lepidoptera, combined with orthologue-level comparisons of chromosomes, we conclude that the ancestral lepidopteran karyotype has been n=31 for at least 140\u2009My. We show that fusion chromosomes have retained the ancestral chromosome segments and very few rearrangements have occurred across the fusion sites. The same, shortest ancestral chromosomes have independently participated in fusion events in species with smaller karyotypes. The short chromosomes have higher rearrangement rate than long ones. These characteristics highlight distinctive features of the evolutionary dynamics of butterflies and moths.", "doi": "10.1038/ncomms5737", "pmid": "25189940", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "ncomms5737"}, {"db": "pmc", "key": "PMC4164777"}, {"db": "mid", "key": "EMS59677"}, {"db": "GENBANK", "key": "APLT00000000"}], "notes": [], "created": "2017-05-04T14:57:08.111Z", "modified": "2017-05-30T14:30:23.346Z"}, {"entity": "publication", "iuid": "1997c4840801487f8f2ff1f6fc46f393", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1997c4840801487f8f2ff1f6fc46f393.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1997c4840801487f8f2ff1f6fc46f393"}}, "title": "Exome sequencing reveals frequent inactivating mutations in ARID1A, ARID1B, ARID2 and ARID4A in microsatellite unstable colorectal cancer.", "authors": [{"family": "Cajuso", "given": "Tatiana", "initials": "T"}, {"family": "H\u00e4nninen", "given": "Ulrika A", "initials": "UA"}, {"family": "Kondelin", "given": "Johanna", "initials": "J"}, {"family": "Gylfe", "given": "Alexandra E", "initials": "AE"}, {"family": "Tanskanen", "given": "Tomas", "initials": "T"}, {"family": "Katainen", "given": "Riku", "initials": "R"}, {"family": "Pitk\u00e4nen", "given": "Esa", "initials": "E"}, {"family": "Ristolainen", "given": "Heikki", "initials": "H"}, {"family": "Kaasinen", "given": "Eevi", "initials": "E"}, {"family": "Taipale", "given": "Minna", "initials": "M"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}, {"family": "B\u00f6hm", "given": "Jan", "initials": "J"}, {"family": "Renkonen-Sinisalo", "given": "Laura", "initials": "L"}, {"family": "Mecklin", "given": "Jukka-Pekka", "initials": "JP"}, {"family": "J\u00e4rvinen", "given": "Heikki", "initials": "H"}, {"family": "Tuupanen", "given": "Sari", "initials": "S"}, {"family": "Kilpivaara", "given": "Outi", "initials": "O"}, {"family": "Vahteristo", "given": "Pia", "initials": "P"}], "type": "journal article", "published": "2014-08-01", "journal": {"volume": "135", "issn": "1097-0215", "issue": "3", "pages": "611-623", "title": "Int. J. Cancer", "issn-l": "0020-7136"}, "abstract": "ARID1A has been identified as a novel tumor suppressor gene in ovarian cancer and subsequently in various other tumor types. ARID1A belongs to the ARID domain containing gene family, which comprises of 15 genes involved, for example, in transcriptional regulation, proliferation and chromatin remodeling. In this study, we used exome sequencing data to analyze the mutation frequency of all the ARID domain containing genes in 25 microsatellite unstable (MSI) colorectal cancers (CRCs) as a first systematic effort to characterize the mutation pattern of the whole ARID gene family. Genes which fulfilled the selection criteria in this discovery set (mutations in at least 4/25 [16%] samples, including at least one nonsense or splice site mutation) were chosen for further analysis in an independent validation set of 21 MSI CRCs. We found that in addition to ARID1A, which was mutated in 39% of the tumors (18/46), also ARID1B (13%, 6/46), ARID2 (13%, 6/46) and ARID4A (20%, 9/46) were frequently mutated. In all these genes, the mutations were distributed along the entire length of the gene, thus distinguishing them from typical MSI target genes previously described. Our results indicate that in addition to ARID1A, other members of the ARID gene family may play a role in MSI CRC.", "doi": "10.1002/ijc.28705", "pmid": "24382590", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:57:07.503Z", "modified": "2017-05-30T11:44:29.242Z"}, {"entity": "publication", "iuid": "83bef43fbe384d24bc0547a849f94ec6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/83bef43fbe384d24bc0547a849f94ec6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/83bef43fbe384d24bc0547a849f94ec6"}}, "title": "Transcriptome analysis reveals signature of adaptation to landscape fragmentation.", "authors": [{"family": "Somervuo", "given": "Panu", "initials": "P"}, {"family": "Kvist", "given": "Jouni", "initials": "J"}, {"family": "Ikonen", "given": "Suvi", "initials": "S"}, {"family": "Auvinen", "given": "Petri", "initials": "P"}, {"family": "Paulin", "given": "Lars", "initials": "L"}, {"family": "Koskinen", "given": "Patrik", "initials": "P"}, {"family": "Holm", "given": "Liisa", "initials": "L"}, {"family": "Taipale", "given": "Minna", "initials": "M"}, {"family": "Duplouy", "given": "Anne", "initials": "A"}, {"family": "Ruokolainen", "given": "Annukka", "initials": "A"}, {"family": "Saarnio", "given": "Suvi", "initials": "S"}, {"family": "Sir\u00e9n", "given": "Jukka", "initials": "J"}, {"family": "Kohonen", "given": "Jukka", "initials": "J"}, {"family": "Corander", "given": "Jukka", "initials": "J"}, {"family": "Frilander", "given": "Mikko J", "initials": "MJ"}, {"family": "Ahola", "given": "Virpi", "initials": "V"}, {"family": "Hanski", "given": "Ilkka", "initials": "I"}], "type": "journal article", "published": "2014-07-02", "journal": {"volume": "9", "issn": "1932-6203", "issue": "7", "pages": "e101467", "title": "PLoS ONE", "issn-l": "1932-6203"}, "abstract": "We characterize allelic and gene expression variation between populations of the Glanville fritillary butterfly (Melitaea cinxia) from two fragmented and two continuous landscapes in northern Europe. The populations exhibit significant differences in their life history traits, e.g. butterflies from fragmented landscapes have higher flight metabolic rate and dispersal rate in the field, and higher larval growth rate, than butterflies from continuous landscapes. In fragmented landscapes, local populations are small and have a high risk of local extinction, and hence the long-term persistence at the landscape level is based on frequent re-colonization of vacant habitat patches, which is predicted to select for increased dispersal rate. Using RNA-seq data and a common garden experiment, we found that a large number of genes (1,841) were differentially expressed between the landscape types. Hexamerin genes, the expression of which has previously been shown to have high heritability and which correlate strongly with larval development time in the Glanville fritillary, had higher expression in fragmented than continuous landscapes. Genes that were more highly expressed in butterflies from newly-established than old local populations within a fragmented landscape were also more highly expressed, at the landscape level, in fragmented than continuous landscapes. This result suggests that recurrent extinctions and re-colonizations in fragmented landscapes select a for specific expression profile. Genes that were significantly up-regulated following an experimental flight treatment had higher basal expression in fragmented landscapes, indicating that these butterflies are genetically primed for frequent flight. Active flight causes oxidative stress, but butterflies from fragmented landscapes were more tolerant of hypoxia. We conclude that differences in gene expression between the landscape types reflect genomic adaptations to landscape fragmentation.", "doi": "10.1371/journal.pone.0101467", "pmid": "24988207", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "PONE-D-14-13404"}, {"db": "pmc", "key": "PMC4079591"}, {"db": "GEO", "key": "GSE47692"}], "notes": [], "created": "2017-05-04T14:57:08.732Z", "modified": "2017-05-30T14:30:27.964Z"}, {"entity": "publication", "iuid": "f3d3e0a90bc74c25a9eb9e2d3740549a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f3d3e0a90bc74c25a9eb9e2d3740549a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f3d3e0a90bc74c25a9eb9e2d3740549a"}}, "title": "A prostate cancer susceptibility allele at 6q22 increases RFX6 expression by modulating HOXB13 chromatin binding.", "authors": [{"family": "Huang", "given": "Qilai", "initials": "Q"}, {"family": "Whitington", "given": "Thomas", "initials": "T"}, {"family": "Gao", "given": "Ping", "initials": "P"}, {"family": "Lindberg", "given": "Johan F", "initials": "JF"}, {"family": "Yang", "given": "Yuehong", "initials": "Y"}, {"family": "Sun", "given": "Jielin", "initials": "J"}, {"family": "V\u00e4is\u00e4nen", "given": "Marja-Riitta", "initials": "MR"}, {"family": "Szulkin", "given": "Robert", "initials": "R"}, {"family": "Annala", "given": "Matti", "initials": "M"}, {"family": "Yan", "given": "Jian", "initials": "J"}, {"family": "Egevad", "given": "Lars A", "initials": "LA"}, {"family": "Zhang", "given": "Kai", "initials": "K"}, {"family": "Lin", "given": "Ruizhu", "initials": "R"}, {"family": "Jolma", "given": "Arttu", "initials": "A"}, {"family": "Nykter", "given": "Matti", "initials": "M"}, {"family": "Manninen", "given": "Aki", "initials": "A"}, {"family": "Wiklund", "given": "Fredrik", "initials": "F"}, {"family": "Vaarala", "given": "Markku H", "initials": "MH"}, {"family": "Visakorpi", "given": "Tapio", "initials": "T"}, {"family": "Xu", "given": "Jianfeng", "initials": "J"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}, {"family": "Wei", "given": "Gong-Hong", "initials": "GH"}], "type": "journal article", "published": "2014-02-00", "journal": {"volume": "46", "issn": "1546-1718", "issue": "2", "pages": "126-135", "title": "Nat. Genet.", "issn-l": "1061-4036"}, "abstract": "Genome-wide association studies have identified thousands of SNPs associated with predisposition to various diseases, including prostate cancer. However, the mechanistic roles of these SNPs remain poorly defined, particularly for noncoding polymorphisms. Here we find that the prostate cancer risk-associated SNP rs339331 at 6q22 lies within a functional HOXB13-binding site. The risk-associated T allele at rs339331 increases binding of HOXB13 to a transcriptional enhancer, conferring allele-specific upregulation of the rs339331-associated gene RFX6. Suppression of RFX6 diminishes prostate cancer cell proliferation, migration and invasion. Clinical data indicate that RFX6 upregulation in human prostate cancers correlates with tumor progression, metastasis and risk of biochemical relapse. Finally, we observe a significant association between the risk-associated T allele at rs339331 and increased RFX6 mRNA levels in human prostate tumors. Together, our results suggest that rs339331 affects prostate cancer risk by altering RFX6 expression through a functional interaction with the prostate cancer susceptibility gene HOXB13.", "doi": "10.1038/ng.2862", "pmid": "24390282", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "ng.2862"}, {"db": "GEO", "key": "GSE21032"}, {"db": "GEO", "key": "GSE3325"}, {"db": "GEO", "key": "GSE35988"}, {"db": "SRA", "key": "SRA014231"}], "notes": [], "created": "2017-05-04T14:57:08.427Z", "modified": "2017-05-30T11:44:40.032Z"}, {"entity": "publication", "iuid": "8bdc034874724611ab7e81f7f3a523c3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8bdc034874724611ab7e81f7f3a523c3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8bdc034874724611ab7e81f7f3a523c3"}}, "title": "Eleven candidate susceptibility genes for common familial colorectal cancer.", "authors": [{"family": "Gylfe", "given": "Alexandra E", "initials": "AE"}, {"family": "Katainen", "given": "Riku", "initials": "R"}, {"family": "Kondelin", "given": "Johanna", "initials": "J"}, {"family": "Tanskanen", "given": "Tomas", "initials": "T"}, {"family": "Cajuso", "given": "Tatiana", "initials": "T"}, {"family": "H\u00e4nninen", "given": "Ulrika", "initials": "U"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}, {"family": "Taipale", "given": "Minna", "initials": "M"}, {"family": "Renkonen-Sinisalo", "given": "Laura", "initials": "L"}, {"family": "J\u00e4rvinen", "given": "Heikki", "initials": "H"}, {"family": "Mecklin", "given": "Jukka-Pekka", "initials": "JP"}, {"family": "Kilpivaara", "given": "Outi", "initials": "O"}, {"family": "Pitk\u00e4nen", "given": "Esa", "initials": "E"}, {"family": "Vahteristo", "given": "Pia", "initials": "P"}, {"family": "Tuupanen", "given": "Sari", "initials": "S"}, {"family": "Karhu", "given": "Auli", "initials": "A"}, {"family": "Aaltonen", "given": "Lauri A", "initials": "LA"}], "type": "journal article", "published": "2013-10-17", "journal": {"volume": "9", "issn": "1553-7404", "issue": "10", "pages": "e1003876", "title": "PLoS Genet.", "issn-l": "1553-7390"}, "abstract": "Hereditary factors are presumed to play a role in one third of colorectal cancer (CRC) cases. However, in the majority of familial CRC cases the genetic basis of predisposition remains unexplained. This is particularly true for families with few affected individuals. To identify susceptibility genes for this common phenotype, we examined familial cases derived from a consecutive series of 1514 Finnish CRC patients. Ninety-six familial CRC patients with no previous diagnosis of a hereditary CRC syndrome were included in the analysis. Eighty-six patients had one affected first-degree relative, and ten patients had two or more. Exome sequencing was utilized to search for genes harboring putative loss-of-function variants, because such alterations are likely candidates for disease-causing mutations. Eleven genes with rare truncating variants in two or three familial CRC cases were identified: UACA, SFXN4, TWSG1, PSPH, NUDT7, ZNF490, PRSS37, CCDC18, PRADC1, MRPL3, and AKR1C4. Loss of heterozygosity was examined in all respective cancer samples, and was detected in seven occasions involving four of the candidate genes. In all seven occasions the wild-type allele was lost (P = 0.0078) providing additional evidence that these eleven genes are likely to include true culprits. The study provides a set of candidate predisposition genes which may explain a subset of common familial CRC. Additional genetic validation in other populations is required to provide firm evidence for causality, as well as to characterize the natural history of the respective phenotypes.", "doi": "10.1371/journal.pgen.1003876", "pmid": "24146633", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "PGENETICS-D-13-01401"}, {"db": "pmc", "key": "PMC3798264"}], "notes": [], "created": "2017-05-04T14:57:06.590Z", "modified": "2017-05-30T14:30:18.659Z"}, {"entity": "publication", "iuid": "6e0af6826e6d4032a7a49441bd18017b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6e0af6826e6d4032a7a49441bd18017b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6e0af6826e6d4032a7a49441bd18017b"}}, "title": "Identification of candidate oncogenes in human colorectal cancers with microsatellite instability.", "authors": [{"family": "Gylfe", "given": "Alexandra E", "initials": "AE"}, {"family": "Kondelin", "given": "Johanna", "initials": "J"}, {"family": "Turunen", "given": "Mikko", "initials": "M"}, {"family": "Ristolainen", "given": "Heikki", "initials": "H"}, {"family": "Katainen", "given": "Riku", "initials": "R"}, {"family": "Pitk\u00e4nen", "given": "Esa", "initials": "E"}, {"family": "Kaasinen", "given": "Eevi", "initials": "E"}, {"family": "Rantanen", "given": "Ville", "initials": "V"}, {"family": "Tanskanen", "given": "Tomas", "initials": "T"}, {"family": "Varjosalo", "given": "Markku", "initials": "M"}, {"family": "Lehtonen", "given": "Heli", "initials": "H"}, {"family": "Palin", "given": "Kimmo", "initials": "K"}, {"family": "Taipale", "given": "Minna", "initials": "M"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}, {"family": "Renkonen-Sinisalo", "given": "Laura", "initials": "L"}, {"family": "J\u00e4rvinen", "given": "Heikki", "initials": "H"}, {"family": "B\u00f6hm", "given": "Jan", "initials": "J"}, {"family": "Mecklin", "given": "Jukka-Pekka", "initials": "JP"}, {"family": "Ristim\u00e4ki", "given": "Ari", "initials": "A"}, {"family": "Kilpivaara", "given": "Outi", "initials": "O"}, {"family": "Tuupanen", "given": "Sari", "initials": "S"}, {"family": "Karhu", "given": "Auli", "initials": "A"}, {"family": "Vahteristo", "given": "Pia", "initials": "P"}, {"family": "Aaltonen", "given": "Lauri A", "initials": "LA"}], "type": "journal article", "published": "2013-09-00", "journal": {"volume": "145", "issn": "1528-0012", "issue": "3", "pages": "540-3.e22", "title": "Gastroenterology", "issn-l": "0016-5085"}, "abstract": "Microsatellite instability can be found in approximately 15% of all colorectal cancers. To detect new oncogenes we sequenced the exomes of 25 colorectal tumors and respective healthy colon tissue. Potential mutation hot spots were confirmed in 15 genes; ADAR, DCAF12L2, GLT1D1, ITGA7, MAP1B, MRGPRX4, PSRC1, RANBP2, RPS6KL1, SNCAIP, TCEAL6, TUBB6, WBP5, VEGFB, and ZBTB2; these were validated in 86\u00a0tumors with microsatellite instability. ZBTB2, RANBP2, and PSRC1 also were found to contain hot spot mutations in the validation set. The form of ZBTB2 associated with colorectal cancer increased cell proliferation. The mutation hot spots might be used to develop personalized tumor profiling and therapy.", "doi": "10.1053/j.gastro.2013.05.015", "pmid": "23684749", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "S0016-5085(13)00747-6"}], "notes": [], "created": "2017-05-04T14:57:06.286Z", "modified": "2017-05-30T11:44:14.625Z"}, {"entity": "publication", "iuid": "001c2c5c3ab14854a718c5ef123f9951", "links": {"self": {"href": "https://publications.scilifelab.se/publication/001c2c5c3ab14854a718c5ef123f9951.json"}, "display": {"href": "https://publications.scilifelab.se/publication/001c2c5c3ab14854a718c5ef123f9951"}}, "title": "Transcription factor binding in human cells occurs in dense clusters formed around cohesin anchor sites.", "authors": [{"family": "Yan", "given": "Jian", "initials": "J"}, {"family": "Enge", "given": "Martin", "initials": "M"}, {"family": "Whitington", "given": "Thomas", "initials": "T"}, {"family": "Dave", "given": "Kashyap", "initials": "K"}, {"family": "Liu", "given": "Jianping", "initials": "J"}, {"family": "Sur", "given": "Inderpreet", "initials": "I"}, {"family": "Schmierer", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-9082-7022", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3ee96f9eb454850be6db3318b28479f.json"}}, {"family": "Jolma", "given": "Arttu", "initials": "A"}, {"family": "Kivioja", "given": "Teemu", "initials": "T"}, {"family": "Taipale", "given": "Minna", "initials": "M"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}], "type": "journal article", "published": "2013-08-15", "journal": {"volume": "154", "issn": "1097-4172", "issue": "4", "pages": "801-813", "title": "Cell", "issn-l": "0092-8674"}, "abstract": "During cell division, transcription factors (TFs) are removed from chromatin twice, during DNA synthesis and during condensation of chromosomes. How TFs can efficiently find their sites following these stages has been unclear. Here, we have analyzed the binding pattern of expressed TFs in human colorectal cancer cells. We find that binding of TFs is highly clustered and that the clusters are enriched in binding motifs for several major TF classes. Strikingly, almost all clusters are formed around cohesin, and loss of cohesin decreases both DNA accessibility and binding of TFs to clusters. We show that cohesin remains bound in S phase, holding the nascent sister chromatids together at the TF cluster sites. Furthermore, cohesin remains bound to the cluster sites when TFs are evicted in early M phase. These results suggest that cohesin-binding functions as a cellular memory that promotes re-establishment of TF clusters after DNA replication and chromatin condensation.", "doi": "10.1016/j.cell.2013.07.034", "pmid": "23953112", "labels": {"Bioinformatics and Expression Analysis (BEA)": null, "Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "S0092-8674(13)00942-2"}, {"db": "GEO", "key": "GSE48448"}, {"db": "GEO", "key": "GSE49402"}], "notes": [], "created": "2017-05-04T14:57:05.169Z", "modified": "2021-07-06T14:42:14.615Z"}, {"entity": "publication", "iuid": "a545c6ba60cb45c2997f9f552360db45", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a545c6ba60cb45c2997f9f552360db45.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a545c6ba60cb45c2997f9f552360db45"}}, "title": "Exome sequencing in diagnostic evaluation of colorectal cancer predisposition in young patients.", "authors": [{"family": "Tanskanen", "given": "Tomas", "initials": "T"}, {"family": "Gylfe", "given": "Alexandra E", "initials": "AE"}, {"family": "Katainen", "given": "Riku", "initials": "R"}, {"family": "Taipale", "given": "Minna", "initials": "M"}, {"family": "Renkonen-Sinisalo", "given": "Laura", "initials": "L"}, {"family": "Mecklin", "given": "Jukka-Pekka", "initials": "JP"}, {"family": "J\u00e4rvinen", "given": "Heikki", "initials": "H"}, {"family": "Tuupanen", "given": "Sari", "initials": "S"}, {"family": "Kilpivaara", "given": "Outi", "initials": "O"}, {"family": "Vahteristo", "given": "Pia", "initials": "P"}, {"family": "Aaltonen", "given": "Lauri A", "initials": "LA"}], "type": "journal article", "published": "2013-06-00", "journal": {"volume": "48", "issn": "1502-7708", "issue": "6", "pages": "672-678", "title": "Scand. J. Gastroenterol.", "issn-l": "0036-5521"}, "abstract": "Early-onset colorectal cancer (CRC), defined here as age of onset less than 40 years, develops frequently in genetically predisposed individuals. Next-generation sequencing is an increasingly available option in the diagnostic workup of suspected hereditary susceptibility, but little is known about the practical feasibility and additional diagnostic yield of the technology in this patient group.\n\nWe analyzed 38 young CRC patients derived from a set of 1514 CRC cases. All 38 tumors had been tested in our laboratory for microsatellite instability (MSI), and Sanger sequencing had been used to screen for MLH1 and MSH2 mutations in MSI cases. Also, gastrointestinal polyposis had been diagnosed clinically and molecularly. Family histories were acquired from national registries. If inherited syndromes had not been diagnosed in routine diagnostic efforts (n = 23), normal tissue DNA was analyzed for mutations in a comprehensive set of high-penetrance genes (MLH1, MSH2, MSH6, PMS2, APC, MUTYH, SMAD4, BMPR1A, LKB1/STK11, and PTEN) by exome sequencing.\n\nCRC predisposition syndromes were confirmed in 42% (16/38) of early-onset CRC patients. Hereditary nonpolyposis colorectal cancer was diagnosed in 12 (32%) patients, familial adenomatous polyposis in three (7.9%), and juvenile polyposis in one (2.6%) patient. Exome sequencing revealed one additional MLH1 mutation. Over half of the patients had advanced cancers (Dukes C or D, 61%, 23/38). The majority of nonsyndromic patients had unaffected first-degree relatives and microsatellite-stable tumors.\n\nMicrosatellite instability positivity or gastrointestinal polyposis characterized all patients with unambiguous highly penetrant germline mutations. In our series, exome sequencing produced little added value in diagnosing the underlying predisposition conditions.", "doi": "10.3109/00365521.2013.783102", "pmid": "23544471", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:57:06.890Z", "modified": "2017-05-30T11:44:21.885Z"}, {"entity": "publication", "iuid": "d1f79dd429bb40c59c2657b442b5b151", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d1f79dd429bb40c59c2657b442b5b151.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d1f79dd429bb40c59c2657b442b5b151"}}, "title": "The mitochondrial and autosomal mutation landscapes of prostate cancer.", "authors": [{"family": "Lindberg", "given": "Johan", "initials": "J"}, {"family": "Mills", "given": "Ian G", "initials": "IG"}, {"family": "Klevebring", "given": "Daniel", "initials": "D"}, {"family": "Liu", "given": "Wennuan", "initials": "W"}, {"family": "Neiman", "given": "M\u00e5rten", "initials": "M"}, {"family": "Xu", "given": "Jianfeng", "initials": "J"}, {"family": "Wikstr\u00f6m", "given": "Pernilla", "initials": "P"}, {"family": "Wiklund", "given": "Peter", "initials": "P"}, {"family": "Wiklund", "given": "Fredrik", "initials": "F"}, {"family": "Egevad", "given": "Lars", "initials": "L"}, {"family": "Gr\u00f6nberg", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2013-04-00", "journal": {"volume": "63", "issn": "1873-7560", "issue": "4", "pages": "702-708", "title": "Eur. Urol.", "issn-l": "0302-2838"}, "abstract": "Prostate cancer (PCa) is the most common cancer in men. PCa is strongly age associated; low death rates in surveillance cohorts call into question the widespread use of surgery, which leads to overtreatment and a reduction in quality of life. There is a great need to increase the understanding of tumor characteristics in the context of disease progression.\n\nTo perform the first multigenome investigation of PCa through analysis of both autosomal and mitochondrial DNA, and to integrate exome sequencing data, and RNA sequencing and copy-number alteration (CNA) data to investigate how various different tumor characteristics, commonly analyzed separately, are interconnected.\n\nExome sequencing was applied to 64 tumor samples from 55 PCa patients with varying stage and grade. Integrated analysis was performed on a core set of 50 tumors from which exome sequencing, CNA, and RNA sequencing data were available.\n\nGenes, mutated at a significantly higher rate relative to a genomic background, were identified. In addition, mitochondrial and autosomal mutation rates were correlated to CNAs and proliferation, assessed as a cell cycle gene expression signature.\n\nGenes not previously reported to be significantly mutated in PCa, such as cell division cycle 27 homolog (Saccharomyces cerevisiae) (CDC27), myeloid/lymphoid or mixed-lineage leukemia 3 (MLL3), lysine (K)-specific demethylase 6A (KDM6A), and kinesin family member 5A (KIF5A) were identified. The mutation rate in the mitochondrial genome was 55 times higher than that of the autosomes. Multilevel analysis demonstrated a tight correlation between high reactive-oxygen exposure, chromosomal damage, high proliferation, and in parallel, a transition from multiclonal indolent primary PCa to monoclonal aggressive disease. As we only performed targeted sequence analysis; copy-number neutral rearrangements recently described for PCa were not accounted for.\n\nThe mitochondrial genome displays an elevated mutation rate compared to the autosomal chromosomes. By integrated analysis, we demonstrated that different tumor characteristics are interconnected, providing an increased understanding of PCa etiology.", "doi": "10.1016/j.eururo.2012.11.053", "pmid": "23265383", "labels": {"National Genomics Infrastructure": null, "NGI Stockholm (Genomics Applications)": null, "Karolinska High Throughput Center (KHTC)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "S0302-2838(12)01438-8"}], "notes": [], "created": "2017-05-04T14:57:05.981Z", "modified": "2020-01-21T13:56:05.375Z"}, {"entity": "publication", "iuid": "522305b2ffdc45d89bbb7b488c012459", "links": {"self": {"href": "https://publications.scilifelab.se/publication/522305b2ffdc45d89bbb7b488c012459.json"}, "display": {"href": "https://publications.scilifelab.se/publication/522305b2ffdc45d89bbb7b488c012459"}}, "title": "Exome sequencing of prostate cancer supports the hypothesis of independent tumour origins.", "authors": [{"family": "Lindberg", "given": "Johan", "initials": "J"}, {"family": "Klevebring", "given": "Daniel", "initials": "D"}, {"family": "Liu", "given": "Wennuan", "initials": "W"}, {"family": "Neiman", "given": "M\u00e5rten", "initials": "M"}, {"family": "Xu", "given": "Jianfeng", "initials": "J"}, {"family": "Wiklund", "given": "Peter", "initials": "P"}, {"family": "Wiklund", "given": "Fredrik", "initials": "F"}, {"family": "Mills", "given": "Ian G", "initials": "IG"}, {"family": "Egevad", "given": "Lars", "initials": "L"}, {"family": "Gr\u00f6nberg", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2013-02-00", "journal": {"volume": "63", "issn": "1873-7560", "issue": "2", "pages": "347-353", "title": "Eur. Urol.", "issn-l": "0302-2838"}, "abstract": "Prostate cancer (PCa) is a clinically and pathologically heterogeneous disease. The rapid development of sequencing technology has the potential to deliver new biomarkers with emphasis on aggressive disease and to revolutionise personalised cancer treatment. However, a prostate harbouring cancer commonly contains multiple separate tumour foci, with the potential to aggravate tumour sampling. The level of intraprostatic tumour heterogeneity remains to be determined.\n\nTo determine the level of intraprostatic tumour heterogeneity through genome-wide, high-resolution profiling of multiple tumour samples from the same individual.\n\nMultiple tumour samples were obtained from four individuals following radical prostatectomy. One individual (SWE-1) contained >70% cancer cells in all tumour samples, whereas the other three (SWE-2 to SWE-4) required the use of laser capture microdissection for tumour cell enrichment. Subsequently, DNA was extracted from all tissue samples, and exome sequencing was performed. All tumour foci of SWE-1 were also profiled using a high-resolution array for the identification of copy number alterations (CNA).\n\nShared somatic high-frequency single nucleotide variants (SNV) and CNAs were used to infer the level of intraprostatic tumour heterogeneity.\n\nNo high-frequency mutations, common for the three tumour samples of SWE-1, were identified. Ten randomly chosen positions were validated with Sanger sequencing in all foci, which verified the exome data. The high level of intraprostatic heterogeneity was consistent in all individuals. In total, three out of four individuals harboured tumours without an apparent common somatic denominator. Although we cannot exclude the presence of common structural rearrangements, a high-density array was used for the detection of deletions and amplifications in SWE-1, which agreed with the exome data.\n\nWe present evidence for the presence of somatically independent tumours within the same prostate. This finding will have implications for personalised cancer treatment and biomarker discovery.", "doi": "10.1016/j.eururo.2012.03.050", "pmid": "22502944", "labels": {"National Genomics Infrastructure": null, "NGI Stockholm (Genomics Applications)": null, "Karolinska High Throughput Center (KHTC)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "S0302-2838(12)00402-2"}], "notes": [], "created": "2017-05-04T14:57:05.469Z", "modified": "2020-01-21T13:56:02.307Z"}, {"entity": "publication", "iuid": "8eea4041c6b445b58bb04c77b59cbe11", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8eea4041c6b445b58bb04c77b59cbe11.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8eea4041c6b445b58bb04c77b59cbe11"}}, "title": "DNA-binding specificities of human transcription factors.", "authors": [{"family": "Jolma", "given": "Arttu", "initials": "A"}, {"family": "Yan", "given": "Jian", "initials": "J"}, {"family": "Whitington", "given": "Thomas", "initials": "T"}, {"family": "Toivonen", "given": "Jarkko", "initials": "J"}, {"family": "Nitta", "given": "Kazuhiro R", "initials": "KR"}, {"family": "Rastas", "given": "Pasi", "initials": "P"}, {"family": "Morgunova", "given": "Ekaterina", "initials": "E"}, {"family": "Enge", "given": "Martin", "initials": "M"}, {"family": "Taipale", "given": "Mikko", "initials": "M"}, {"family": "Wei", "given": "Gonghong", "initials": "G"}, {"family": "Palin", "given": "Kimmo", "initials": "K"}, {"family": "Vaquerizas", "given": "Juan M", "initials": "JM"}, {"family": "Vincentelli", "given": "Renaud", "initials": "R"}, {"family": "Luscombe", "given": "Nicholas M", "initials": "NM"}, {"family": "Hughes", "given": "Timothy R", "initials": "TR"}, {"family": "Lemaire", "given": "Patrick", "initials": "P"}, {"family": "Ukkonen", "given": "Esko", "initials": "E"}, {"family": "Kivioja", "given": "Teemu", "initials": "T"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}], "type": "journal article", "published": "2013-01-17", "journal": {"volume": "152", "issn": "1097-4172", "issue": "1-2", "pages": "327-339", "title": "Cell", "issn-l": "0092-8674"}, "abstract": "Although the proteins that read the gene regulatory code, transcription factors (TFs), have been largely identified, it is not well known which sequences TFs can recognize. We have analyzed the sequence-specific binding of human TFs using high-throughput SELEX and ChIP sequencing. A total of 830 binding profiles were obtained, describing 239 distinctly different binding specificities. The models represent the majority of human TFs, approximately doubling the coverage compared to existing systematic studies. Our results reveal additional specificity determinants for a large number of factors for which a partial specificity was known, including a commonly observed A- or T-rich stretch that flanks the core motifs. Global analysis of the data revealed that homodimer orientation and spacing preferences, and base-stacking interactions, have a larger role in TF-DNA binding than previously appreciated. We further describe a binding model incorporating these features that is required to understand binding of TFs to DNA.", "doi": "10.1016/j.cell.2012.12.009", "pmid": "23332764", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "S0092-8674(12)01496-1"}], "notes": [], "created": "2017-05-04T14:57:04.866Z", "modified": "2017-05-31T08:13:20.430Z"}, {"entity": "publication", "iuid": "e164267f0e424c6aa7552763809abd16", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e164267f0e424c6aa7552763809abd16.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e164267f0e424c6aa7552763809abd16"}}, "title": "Mice lacking a Myc enhancer that includes human SNP rs6983267 are resistant to intestinal tumors.", "authors": [{"family": "Sur", "given": "Inderpreet Kaur", "initials": "IK"}, {"family": "Hallikas", "given": "Outi", "initials": "O"}, {"family": "V\u00e4h\u00e4rautio", "given": "Anna", "initials": "A"}, {"family": "Yan", "given": "Jian", "initials": "J"}, {"family": "Turunen", "given": "Mikko", "initials": "M"}, {"family": "Enge", "given": "Martin", "initials": "M"}, {"family": "Taipale", "given": "Minna", "initials": "M"}, {"family": "Karhu", "given": "Auli", "initials": "A"}, {"family": "Aaltonen", "given": "Lauri A", "initials": "LA"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}], "type": "journal article", "published": "2012-12-07", "journal": {"volume": "338", "issn": "1095-9203", "issue": "6112", "pages": "1360-1363", "title": "Science", "issn-l": "0036-8075"}, "abstract": "Multiple cancer-associated single-nucleotide polymorphisms (SNPs) have been mapped to conserved sequences within a 500-kilobase region upstream of the MYC oncogene on human chromosome 8q24. These SNPs may affect cancer development through altered regulation of MYC expression, but this hypothesis has been difficult to confirm. We generated mice deficient in Myc-335, a putative MYC regulatory element that contains rs6983267, a SNP accounting for more human cancer-related morbidity than any other genetic variant or mutation. In Myc-335 null mice, Myc transcripts were expressed in the intestinal crypts in a pattern similar to that in wild-type mice but at modestly reduced levels. The mutant mice displayed no overt phenotype but were markedly resistant to intestinal tumorigenesis induced by the APCmin mutation. These results establish that a cancer-associated SNP identified in human genome-wide association studies has a functional effect in vivo.", "doi": "10.1126/science.1228606", "pmid": "23118011", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "science.1228606"}], "notes": [], "created": "2017-05-04T14:57:04.565Z", "modified": "2017-05-30T11:44:06.260Z"}, {"entity": "publication", "iuid": "e490d3539f1c41958d66025d3d2768d9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e490d3539f1c41958d66025d3d2768d9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e490d3539f1c41958d66025d3d2768d9"}}, "title": "Insights into p53 transcriptional function via genome-wide chromatin occupancy and gene expression analysis.", "authors": [{"family": "Nikulenkov", "given": "F", "initials": "F"}, {"family": "Spinnler", "given": "C", "initials": "C"}, {"family": "Li", "given": "H", "initials": "H"}, {"family": "Tonelli", "given": "C", "initials": "C"}, {"family": "Shi", "given": "Y", "initials": "Y"}, {"family": "Turunen", "given": "M", "initials": "M"}, {"family": "Kivioja", "given": "T", "initials": "T"}, {"family": "Ignatiev", "given": "I", "initials": "I"}, {"family": "Kel", "given": "A", "initials": "A"}, {"family": "Taipale", "given": "J", "initials": "J"}, {"family": "Selivanova", "given": "G", "initials": "G"}], "type": "journal article", "published": "2012-12-00", "journal": {"volume": "19", "issn": "1476-5403", "issue": "12", "pages": "1992-2002", "title": "Cell Death Differ.", "issn-l": "1350-9047"}, "abstract": "The tumor-suppressor p53 can induce various biological responses. Yet, it is not clear whether it is p53 in vivo promoter selectivity that triggers different transcription programs leading to different outcomes. Our analysis of genome-wide chromatin occupancy by p53 using chromatin immunoprecipitation (ChIP)-seq revealed 'p53 default program', that is, the pattern of major p53-bound sites that is similar upon p53 activation by nutlin3a, reactivation of p53 and induction of tumor cell apoptosis (RITA) or 5-fluorouracil in breast cancer cells, despite different biological outcomes. Parallel analysis of gene expression allowed identification of 280 novel p53 target genes, including p53-repressed AURKA. We identified Sp1 as one of the p53 modulators, which confer specificity to p53-mediated transcriptional response upon RITA. Further, we found that STAT3 antagonizes p53-mediated repression of a subset of genes, including AURKA.", "doi": "10.1038/cdd.2012.89", "pmid": "22790872", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "cdd201289"}, {"db": "pmc", "key": "PMC3504713"}], "notes": [], "created": "2017-05-04T14:57:04.267Z", "modified": "2017-05-30T11:44:02.670Z"}, {"entity": "publication", "iuid": "0318de93d4474776aa4f1b4e4769dc0e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0318de93d4474776aa4f1b4e4769dc0e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0318de93d4474776aa4f1b4e4769dc0e"}}, "title": "Counting absolute numbers of molecules using unique molecular identifiers.", "authors": [{"family": "Kivioja", "given": "Teemu", "initials": "T"}, {"family": "V\u00e4h\u00e4rautio", "given": "Anna", "initials": "A"}, {"family": "Karlsson", "given": "Kasper", "initials": "K"}, {"family": "Bonke", "given": "Martin", "initials": "M"}, {"family": "Enge", "given": "Martin", "initials": "M"}, {"family": "Linnarsson", "given": "Sten", "initials": "S"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}], "type": "journal article", "published": "2011-11-20", "journal": {"volume": "9", "issn": "1548-7105", "issue": "1", "pages": "72-74", "title": "Nat. Methods", "issn-l": "1548-7091"}, "abstract": "Counting individual RNA or DNA molecules is difficult because they are hard to copy quantitatively for detection. To overcome this limitation, we applied unique molecular identifiers (UMIs), which make each molecule in a population distinct, to genome-scale human karyotyping and mRNA sequencing in Drosophila melanogaster. Use of this method can improve accuracy of almost any next-generation sequencing method, including chromatin immunoprecipitation-sequencing, genome assembly, diagnostics and manufacturing-process control and monitoring.", "doi": "10.1038/nmeth.1778", "pmid": "22101854", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "nmeth.1778"}], "notes": [], "created": "2017-05-04T14:57:03.362Z", "modified": "2017-05-30T14:30:09.110Z"}, {"entity": "publication", "iuid": "6754e5e0fbbb4d85bc5707ec87f99a76", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6754e5e0fbbb4d85bc5707ec87f99a76.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6754e5e0fbbb4d85bc5707ec87f99a76"}}, "title": "MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas.", "authors": [{"family": "M\u00e4kinen", "given": "Netta", "initials": "N"}, {"family": "Mehine", "given": "Miika", "initials": "M"}, {"family": "Tolvanen", "given": "Jaana", "initials": "J"}, {"family": "Kaasinen", "given": "Eevi", "initials": "E"}, {"family": "Li", "given": "Yilong", "initials": "Y"}, {"family": "Lehtonen", "given": "Heli J", "initials": "HJ"}, {"family": "Gentile", "given": "Massimiliano", "initials": "M"}, {"family": "Yan", "given": "Jian", "initials": "J"}, {"family": "Enge", "given": "Martin", "initials": "M"}, {"family": "Taipale", "given": "Minna", "initials": "M"}, {"family": "Aavikko", "given": "Mervi", "initials": "M"}, {"family": "Katainen", "given": "Riku", "initials": "R"}, {"family": "Virolainen", "given": "Elina", "initials": "E"}, {"family": "B\u00f6hling", "given": "Tom", "initials": "T"}, {"family": "Koski", "given": "Taru A", "initials": "TA"}, {"family": "Launonen", "given": "Virpi", "initials": "V"}, {"family": "Sj\u00f6berg", "given": "Jari", "initials": "J"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}, {"family": "Vahteristo", "given": "Pia", "initials": "P"}, {"family": "Aaltonen", "given": "Lauri A", "initials": "LA"}], "type": "journal article", "published": "2011-10-14", "journal": {"volume": "334", "issn": "1095-9203", "issue": "6053", "pages": "252-255", "title": "Science", "issn-l": "0036-8075"}, "abstract": "Uterine leiomyomas, or fibroids, are benign tumors that affect millions of women worldwide and that can cause considerable morbidity. To study the genetic basis of this tumor type, we examined 18 uterine leiomyomas derived from 17 different patients by exome sequencing and identified tumor-specific mutations in the mediator complex subunit 12 (MED12) gene in 10. Through analysis of 207 additional tumors, we determined that MED12 is altered in 70% (159 of 225) of tumors from a total of 80 patients. The Mediator complex is a 26-subunit transcriptional regulator that bridges DNA regulatory sequences to the RNA polymerase II initiation complex. All mutations resided in exon 2, suggesting that aberrant function of this region of MED12 contributes to tumorigenesis.", "doi": "10.1126/science.1208930", "pmid": "21868628", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "science.1208930"}, {"db": "GEO", "key": "GSE30673"}], "notes": [], "created": "2017-05-04T14:57:03.662Z", "modified": "2017-05-30T11:43:55.439Z"}, {"entity": "publication", "iuid": "ca045d3361f44f1c9dd7e9248c4c1e98", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ca045d3361f44f1c9dd7e9248c4c1e98.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ca045d3361f44f1c9dd7e9248c4c1e98"}}, "title": "Methods for Analysis of Transcription Factor DNA-Binding Specificity In Vitro.", "authors": [{"family": "Jolma", "given": "Arttu", "initials": "A"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}], "type": "journal article", "published": "2011-05-11", "journal": {"volume": "52", "issn": "0306-0225", "issue": null, "pages": "155-173", "title": "Subcell. Biochem.", "issn-l": null}, "abstract": "Transcription of genes during development and in response to environmental stimuli is determined by genomic DNA sequence. The DNA sequences regulating transcription are read by sequence-specific transcription factors (TFs) that recognize relatively short sequences, generally between four and twenty base pairs in length. Transcriptional regulation generally requires binding of multiple TFs in close proximity to each other. Mechanistic understanding of transcription in an organism thus requires detailed knowledge of binding affinities of all its TFs to all possible DNA sequences, and the co-operative interactions between the TFs. However, very little is known about such co-operative binding interactions, and even the simple TF-DNA binding information exists only for a very small proportion of all TFs - for example, mammals have approximately 1,300-2,000 TFs [1, 2], yet the largest public databases for TF binding specificity, Jaspar and Uniprobe [3, 4] currently list only approximately 500 moderate to high resolution profiles for human or mouse. This lack of knowledge is in part due to the fact that analysis of TF DNA binding has been laborious and expensive. In this chapter, we review methods that can be used to determine binding specificity of TFs to DNA, mainly focusing on recently developed assays that allow high-resolution analysis of TF binding specificity in relatively high throughput.", "doi": "10.1007/978-90-481-9069-0_7", "pmid": "21557082", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:57:03.967Z", "modified": "2017-05-30T11:43:59.054Z"}, {"entity": "publication", "iuid": "24677996eddc4304aa29e96d2a9e9948", "links": {"self": {"href": "https://publications.scilifelab.se/publication/24677996eddc4304aa29e96d2a9e9948.json"}, "display": {"href": "https://publications.scilifelab.se/publication/24677996eddc4304aa29e96d2a9e9948"}}, "title": "Genome-wide analysis of ETS-family DNA-binding in vitro and in vivo.", "authors": [{"family": "Wei", "given": "Gong-Hong", "initials": "GH"}, {"family": "Badis", "given": "Gwenael", "initials": "G"}, {"family": "Berger", "given": "Michael F", "initials": "MF"}, {"family": "Kivioja", "given": "Teemu", "initials": "T"}, {"family": "Palin", "given": "Kimmo", "initials": "K"}, {"family": "Enge", "given": "Martin", "initials": "M"}, {"family": "Bonke", "given": "Martin", "initials": "M"}, {"family": "Jolma", "given": "Arttu", "initials": "A"}, {"family": "Varjosalo", "given": "Markku", "initials": "M"}, {"family": "Gehrke", "given": "Andrew R", "initials": "AR"}, {"family": "Yan", "given": "Jian", "initials": "J"}, {"family": "Talukder", "given": "Shaheynoor", "initials": "S"}, {"family": "Turunen", "given": "Mikko", "initials": "M"}, {"family": "Taipale", "given": "Mikko", "initials": "M"}, {"family": "Stunnenberg", "given": "Hendrik G", "initials": "HG"}, {"family": "Ukkonen", "given": "Esko", "initials": "E"}, {"family": "Hughes", "given": "Timothy R", "initials": "TR"}, {"family": "Bulyk", "given": "Martha L", "initials": "ML"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}], "type": "journal article", "published": "2010-07-07", "journal": {"volume": "29", "issn": "1460-2075", "issue": "13", "pages": "2147-2160", "title": "EMBO J.", "issn-l": "0261-4189"}, "abstract": "Members of the large ETS family of transcription factors (TFs) have highly similar DNA-binding domains (DBDs)-yet they have diverse functions and activities in physiology and oncogenesis. Some differences in DNA-binding preferences within this family have been described, but they have not been analysed systematically, and their contributions to targeting remain largely uncharacterized. We report here the DNA-binding profiles for all human and mouse ETS factors, which we generated using two different methods: a high-throughput microwell-based TF DNA-binding specificity assay, and protein-binding microarrays (PBMs). Both approaches reveal that the ETS-binding profiles cluster into four distinct classes, and that all ETS factors linked to cancer, ERG, ETV1, ETV4 and FLI1, fall into just one of these classes. We identify amino-acid residues that are critical for the differences in specificity between all the classes, and confirm the specificities in vivo using chromatin immunoprecipitation followed by sequencing (ChIP-seq) for a member of each class. The results indicate that even relatively small differences in in vitro binding specificity of a TF contribute to site selectivity in vivo.", "doi": "10.1038/emboj.2010.106", "pmid": "20517297", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "emboj2010106"}, {"db": "pmc", "key": "PMC2905244"}], "notes": [], "created": "2017-05-04T14:57:02.756Z", "modified": "2017-05-30T11:43:48.260Z"}, {"entity": "publication", "iuid": "19180cd5e1594314be45d213828fa5ac", "links": {"self": {"href": "https://publications.scilifelab.se/publication/19180cd5e1594314be45d213828fa5ac.json"}, "display": {"href": "https://publications.scilifelab.se/publication/19180cd5e1594314be45d213828fa5ac"}}, "title": "Multiplexed massively parallel SELEX for characterization of human transcription factor binding specificities.", "authors": [{"family": "Jolma", "given": "Arttu", "initials": "A"}, {"family": "Kivioja", "given": "Teemu", "initials": "T"}, {"family": "Toivonen", "given": "Jarkko", "initials": "J"}, {"family": "Cheng", "given": "Lu", "initials": "L"}, {"family": "Wei", "given": "Gonghong", "initials": "G"}, {"family": "Enge", "given": "Martin", "initials": "M"}, {"family": "Taipale", "given": "Mikko", "initials": "M"}, {"family": "Vaquerizas", "given": "Juan M", "initials": "JM"}, {"family": "Yan", "given": "Jian", "initials": "J"}, {"family": "Sillanp\u00e4\u00e4", "given": "Mikko J", "initials": "MJ"}, {"family": "Bonke", "given": "Martin", "initials": "M"}, {"family": "Palin", "given": "Kimmo", "initials": "K"}, {"family": "Talukder", "given": "Shaheynoor", "initials": "S"}, {"family": "Hughes", "given": "Timothy R", "initials": "TR"}, {"family": "Luscombe", "given": "Nicholas M", "initials": "NM"}, {"family": "Ukkonen", "given": "Esko", "initials": "E"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}], "type": "journal article", "published": "2010-06-00", "journal": {"volume": "20", "issn": "1549-5469", "issue": "6", "pages": "861-873", "title": "Genome Res.", "issn-l": "1088-9051"}, "abstract": "The genetic code-the binding specificity of all transfer-RNAs--defines how protein primary structure is determined by DNA sequence. DNA also dictates when and where proteins are expressed, and this information is encoded in a pattern of specific sequence motifs that are recognized by transcription factors. However, the DNA-binding specificity is only known for a small fraction of the approximately 1400 human transcription factors (TFs). We describe here a high-throughput method for analyzing transcription factor binding specificity that is based on systematic evolution of ligands by exponential enrichment (SELEX) and massively parallel sequencing. The method is optimized for analysis of large numbers of TFs in parallel through the use of affinity-tagged proteins, barcoded selection oligonucleotides, and multiplexed sequencing. Data are analyzed by a new bioinformatic platform that uses the hundreds of thousands of sequencing reads obtained to control the quality of the experiments and to generate binding motifs for the TFs. The described technology allows higher throughput and identification of much longer binding profiles than current microarray-based methods. In addition, as our method is based on proteins expressed in mammalian cells, it can also be used to characterize DNA-binding preferences of full-length proteins or proteins requiring post-translational modifications. We validate the method by determining binding specificities of 14 different classes of TFs and by confirming the specificities for NFATC1 and RFX3 using ChIP-seq. Our results reveal unexpected dimeric modes of binding for several factors that were thought to preferentially bind DNA as monomers.", "doi": "10.1101/gr.100552.109", "pmid": "20378718", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null, "Karolinska High Throughput Center (KHTC)": null}, "xrefs": [{"db": "pii", "key": "gr.100552.109"}, {"db": "pmc", "key": "PMC2877582"}], "notes": [], "created": "2017-05-04T14:57:03.059Z", "modified": "2020-01-21T13:56:00.915Z"}]}