{"entity": "journal", "iuid": "8bfc66f97ec04a2ba30924ee8ceafaae", "timestamp": "2026-08-15T12:54:35.659Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Epigenetics.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Epigenetics"}}, "title": "Epigenetics", "issn": "1559-2308", "issn-l": "1559-2294", "publications_count": 20, "publications": [{"entity": "publication", "iuid": "ba84364ff43d4dcdaf6b28d76f58c594", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ba84364ff43d4dcdaf6b28d76f58c594.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ba84364ff43d4dcdaf6b28d76f58c594"}}, "title": "An enriched maternal environment and stereotypies of sows differentially affect the neuro-epigenome of brain regions related to emotionality in their piglets.", "authors": [{"family": "Tatemoto", "given": "Patricia", "initials": "P"}, {"family": "P\u00e9rtille", "given": "F\u00e1bio", "initials": "F"}, {"family": "Bernardino", "given": "Thiago", "initials": "T"}, {"family": "Zanella", "given": "Ricardo", "initials": "R"}, {"family": "Guerrero-Bosagna", "given": "Carlos", "initials": "C"}, {"family": "Zanella", "given": "Adroaldo Jos\u00e9", "initials": "AJ"}], "type": "journal article", "published": "2023-12-00", "journal": {"title": "Epigenetics", "issn": "1559-2308", "volume": "18", "issue": "1", "pages": "2196656", "issn-l": "1559-2294"}, "abstract": "Epigenetic mechanisms are important modulators of neurodevelopmental outcomes in the offspring of animals challenged during pregnancy. Pregnant sows living in a confined environment are challenged with stress and lack of stimulation which may result in the expression of stereotypies (repetitive behaviours without an apparent function). Little attention has been devoted to the postnatal effects of maternal stereotypies in the offspring. We investigated how the environment and stereotypies of pregnant sows affected the neuro-epigenome of their piglets. We focused on the amygdala, frontal cortex, and hippocampus, brain regions related to emotionality, learning, memory, and stress response. Differentially methylated regions (DMRs) were investigated in these brain regions of male piglets born from sows kept in an enriched vs a barren environment. Within the latter group of piglets, we compared the brain methylomes of piglets born from sows expressing stereotypies vs sows not expressing stereotypies. DMRs emerged in each comparison. While the epigenome of the hippocampus and frontal cortex of piglets is mainly affected by the maternal environment, the epigenome of the amygdala is mainly affected by maternal stereotypies. The molecular pathways and mechanisms triggered in the brains of piglets by maternal environment or stereotypies are different, which is reflected on the differential gene function associated to the DMRs found in each piglets' brain region . The present study is the first to investigate the neuro-epigenomic effects of maternal enrichment in pigs' offspring and the first to investigate the neuro-epigenomic effects of maternal stereotypies in the offspring of a mammal.", "doi": "10.1080/15592294.2023.2196656", "pmid": "37192378", "labels": {"NGI Short read": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10190189"}], "notes": [], "created": "2023-10-11T12:33:45.733Z", "modified": "2024-01-16T13:48:31.582Z"}, {"entity": "publication", "iuid": "c02d8f92e64b4166ac3dc11da08b0eaa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c02d8f92e64b4166ac3dc11da08b0eaa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c02d8f92e64b4166ac3dc11da08b0eaa"}}, "title": "An epigenome-wide analysis of sex hormone levels and DNA methylation in male blood samples.", "authors": [{"family": "Harbs", "given": "Justin", "initials": "J"}, {"family": "Rinaldi", "given": "Sabina", "initials": "S"}, {"family": "Keski-Rahkonen", "given": "Pekka", "initials": "P"}, {"family": "Liu", "given": "Xijia", "initials": "X"}, {"family": "Palmqvist", "given": "Richard", "initials": "R"}, {"family": "Van Guelpen", "given": "Bethany", "initials": "B"}, {"family": "Harlid", "given": "Sophia", "initials": "S"}], "type": "journal article", "published": "2023-12-00", "journal": {"title": "Epigenetics", "issn": "1559-2308", "volume": "18", "issue": "1", "pages": "2196759", "issn-l": "1559-2294"}, "abstract": "Endogenous sex hormones and DNA methylation both play important roles in various diseases. However, their interplay is largely unknown. A deeper understanding of their interrelationships could provide new insights into the pathology of disease development. We, therefore, investigated associations between circulating sex hormones, sex hormone binding globulin (SHBG), and DNA methylation in blood, using samples from 77 men (65 with repeated samples), from the population-based Northern Sweden Health and Disease Study (NSHDS). DNA methylation was measured in buffy coat using the Infinium Methylation EPIC BeadChip (Illumina). Sex hormone (oestradiol, oestrone, testosterone, androstenedione, dehydroepiandrosterone, and progesterone) and SHBG concentrations were measured in plasma using a high-performance liquid chromatography tandem mass spectrometry (LC/MS-MS) method and an enzyme-linked immunoassay, respectively. Associations between sex hormones, SHBG, and DNA methylation were estimated using both linear regression and mixed-effects models. Additionally, we used the comb-p method to identify differentially methylated regions based on nearby P values. We identified one novel CpG site (cg14319657), at which DNA methylation was associated with dehydroepiandrosterone, surpassing a genome-wide significance level. In addition, more than 40 differentially methylated regions were associated with levels of sex hormones and SHBG and several of these mapped to genes involved in hormone-related diseases. Our findings support a relationship between circulating sex hormones and DNA methylation and suggest that further investigation is warranted, both for validation, further exploration and to gain a deeper understanding of the mechanisms and potential consequences for health and disease.", "doi": "10.1080/15592294.2023.2196759", "pmid": "36994855", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "NGI SNP genotyping": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10072117"}], "notes": [], "created": "2023-04-06T13:49:55.228Z", "modified": "2023-04-06T13:49:55.241Z"}, {"entity": "publication", "iuid": "044cd2cc0a644d81948691614fa8c89b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/044cd2cc0a644d81948691614fa8c89b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/044cd2cc0a644d81948691614fa8c89b"}}, "title": "Leukocyte DNA methylation in Alzheimer\u00b4s disease associated genes: replication of findings from neuronal cells.", "authors": [{"family": "Karlsson", "given": "Ida K", "initials": "IK", "orcid": "0000-0003-3605-7829", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2c87ada82ae43df9753a891305ddb40.json"}}, {"family": "Ploner", "given": "Alexander", "initials": "A"}, {"family": "Wang", "given": "Yunzhang", "initials": "Y"}, {"family": "Gatz", "given": "Margaret", "initials": "M"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S"}], "type": "journal article", "published": "2022-12-26", "journal": {"title": "Epigenetics", "issn": "1559-2308", "pages": "1-5", "issn-l": "1559-2294"}, "abstract": "Differences in gene-wide DNA methylation of the Alzheimer's disease (AD)-associated genes BIN1, HLA-DRB5, SORL1, SLC24A4, and ABCA7 are reported to be associated with AD in post-mortem brain samples. We investigated whether the same associations could be found in leukocytes collected pre-mortem. Using cohort data of 544 Swedish twins (204 dementia diagnoses), we replicated the findings in HLA-DRB5 and SLC24A4 at P < 0.05. However, co-twin control analyses indicated that the associations were partly explained by familial confounding. Thus, DNA methylation differences in HLA-DRB5 and SLC24A4 are present in both neuronal cells and leukocytes, and not fully explained familial factors.", "doi": "10.1080/15592294.2022.2158285", "pmid": "36573011", "labels": {"NGI SNP genotyping": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [], "notes": [], "created": "2023-01-07T19:43:44.639Z", "modified": "2023-01-19T07:58:14.561Z"}, {"entity": "publication", "iuid": "e2e0b1cdb60c40dabbccb4597711b1ea", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e2e0b1cdb60c40dabbccb4597711b1ea.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e2e0b1cdb60c40dabbccb4597711b1ea"}}, "title": "Comparison of EM-seq and PBAT methylome library methods for low-input DNA.", "authors": [{"family": "Han", "given": "Yanan", "initials": "Y", "orcid": "0000-0002-3464-2656", "researcher": {"href": "https://publications.scilifelab.se/researcher/9dbd01317d224156a002d298de5112ac.json"}}, {"family": "Zheleznyakova", "given": "Galina Yurevna", "initials": "GY"}, {"family": "Marincevic-Zuniga", "given": "Yanara", "initials": "Y"}, {"family": "Kakhki", "given": "Majid Pahlevan", "initials": "MP"}, {"family": "Raine", "given": "Amanda", "initials": "A"}, {"family": "Needhamsen", "given": "Maria", "initials": "M"}, {"family": "Jagodic", "given": "Maja", "initials": "M"}], "type": "journal article", "published": "2021-11-17", "journal": {"title": "Epigenetics", "issn": "1559-2308", "issn-l": "1559-2294", "volume": "17", "issue": "10", "pages": "1195-1204"}, "abstract": "DNA methylation is the most studied epigenetic mark involved in regulation of gene expression. For low input samples, a limited number of methods for quantifying DNA methylation genome-wide has been evaluated. Here, we compared a series of input DNA amounts (1-10ng) from two methylome library preparation protocols, enzymatic methyl-seq (EM-seq) and post-bisulfite adaptor tagging (PBAT) adapted from single-cell PBAT. EM-seq takes advantage of enzymatic activity while PBAT relies on conventional bisulfite conversion for detection of DNA methylation. We found that both methods accurately quantified DNA methylation genome-wide. They produced expected distribution patterns around genomic features, high C-T transition efficiency at non-CpG sites and high correlation between input amounts. However, EM-seq performed better in regard to library and sequencing quality, i.e. EM-seq produced larger insert sizes, higher alignment rates and higher library complexity with lower duplication rate compared to PBAT. Moreover, EM-seq demonstrated higher CpG coverage, better CpG site overlap and higher consistency between input series. In summary, our data suggests that EM-seq overall performed better than PBAT in whole-genome methylation quantification of low input samples.", "doi": "10.1080/15592294.2021.1997406", "pmid": "34709110", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "National Genomics Infrastructure": "Collaborative", "NGI Short read": "Collaborative"}, "xrefs": [], "notes": [], "created": "2021-12-10T11:22:58.275Z", "modified": "2022-11-29T09:19:22.428Z"}, {"entity": "publication", "iuid": "ef732b8cd0214be1887c4a57bb492c04", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ef732b8cd0214be1887c4a57bb492c04.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ef732b8cd0214be1887c4a57bb492c04"}}, "title": "Epigenome-wide cross-tissue correlation of human bone and blood DNA methylation - can blood be used as a surrogate for bone?", "authors": [{"family": "Ebrahimi", "given": "Parvaneh", "initials": "P"}, {"family": "Luthman", "given": "Holger", "initials": "H"}, {"family": "McGuigan", "given": "Fiona E", "initials": "FE", "orcid": "0000-0002-8033-9981", "researcher": {"href": "https://publications.scilifelab.se/researcher/1cf48c3c6f71416799fca5100de388f5.json"}}, {"family": "Akesson", "given": "Kristina E", "initials": "KE"}], "type": "journal article", "published": "2021-01-00", "journal": {"title": "Epigenetics", "issn": "1559-2308", "volume": "16", "issue": "1", "pages": "92-105", "issn-l": "1559-2294"}, "abstract": "Difficulty in obtaining bone tissue is an obstacle to studying epigenetics to understand gene-environment interactions, and their role in disease pathogenesis. Blood is an obvious alternative and in this proof of principle study, our aim was to systematically investigate whether blood is a viable surrogate for bone. We measured epigenome-wide DNA methylation at 850 K CpG sites in matched trabecular bone and peripheral blood collected from the same patients at the same time-point (n = 12 women; 66-85y), to investigate the between-tissue correspondence. What constituted a CpG site with corresponding methylation in both tissues was stringently defined. Only sites highly correlated (r2 > 0.74; FDR q-value <0.05) and at least 80% similarity in methylation level (\u0394\u03b2 <0.2) between paired samples were retained. In total, 28,549 CpG sites were similarly methylated in bone and blood. Between 33% and 49% of loci associated with bone phenotypes through GWAS were represented among these sites, and major pathways relevant to bone regulation were enriched. The results from this study indicate that blood can mirror the bone methylome and capture sites related to bone regulation. This study shows that in principal, peripheral blood is a feasible surrogate for bone tissue in DNA methylation investigations. As the first step, this will provide a platform for future studies in bone epigenetics, and possibly for larger-scale epidemiological studies.", "doi": "10.1080/15592294.2020.1788325", "pmid": "32692944", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7889104"}, {"db": "figshare", "key": "10.6084/m9.figshare.12851657.v1"}], "notes": [], "created": "2020-08-04T14:50:03.380Z", "modified": "2021-11-10T12:49:08.153Z"}, {"entity": "publication", "iuid": "befd645e5e764eac97f5d53eb795294d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/befd645e5e764eac97f5d53eb795294d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/befd645e5e764eac97f5d53eb795294d"}}, "title": "Comparative analysis of genome-wide DNA methylation in Neurospora.", "authors": [{"family": "Hosseini", "given": "Sara", "initials": "S"}, {"family": "Meunier", "given": "C\u00e9cile", "initials": "C"}, {"family": "Nguyen", "given": "Diem", "initials": "D"}, {"family": "Reimeg\u00e5rd", "given": "Johan", "initials": "J"}, {"family": "Johannesson", "given": "Hanna", "initials": "H", "orcid": "0000-0001-6359-9856", "researcher": {"href": "https://publications.scilifelab.se/researcher/36e8fe278e01470e8cddaaccc5dad596.json"}}], "type": "journal article", "published": "2020-09-00", "journal": {"title": "Epigenetics", "issn": "1559-2308", "volume": "15", "issue": "9", "pages": "972-987", "issn-l": "1559-2294"}, "abstract": "DNA methylation is an epigenetic mark that plays an important role in genetic regulation in eukaryotes. Major progress has been made in dissecting the molecular pathways that regulate DNA methylation. Yet, little is known about DNA methylation variation over evolutionary time. Here we present an investigation of the variation of DNA methylation and transposable element (TE) content in species of the filamentous ascomycetes Neurospora. We generated genome-wide DNA methylation data at single-base resolution, together with genomic TE content and gene expression data, of 10 individuals representing five closely related Neurospora species. We found that the methylation levels were low (ranging from 1.3% to 2.5%) and varied among the genomes in a species-specific way. Furthermore, we found that the TEs over 400 bp long were targeted by DNA methylation, and in all genomes, high methylation correlated with low GC, confirming a conserved link between DNA methylation and Repeat Induced Point (RIP) mutations in this group of fungi. Both TE content and DNA methylation pattern showed phylogenetic signal, and the species with the highest TE load (N. crassa) also exhibited the highest methylation level per TE. Our results suggest that DNA methylation is an evolvable trait and indicate that the genomes of Neurospora are shaped by an evolutionary arms race between TEs and host defence.", "doi": "10.1080/15592294.2020.1741758", "pmid": "32228351", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7518705"}], "notes": [], "created": "2020-04-23T08:47:49.215Z", "modified": "2024-01-16T13:48:41.837Z"}, {"entity": "publication", "iuid": "be5bf1b1f6ab471bbecf5c58227c4a16", "links": {"self": {"href": "https://publications.scilifelab.se/publication/be5bf1b1f6ab471bbecf5c58227c4a16.json"}, "display": {"href": "https://publications.scilifelab.se/publication/be5bf1b1f6ab471bbecf5c58227c4a16"}}, "title": "A regulatory role for CHD2 in myelopoiesis.", "authors": [{"family": "Shahin Varnoosfaderani", "given": "Farzaneh", "initials": "F"}, {"family": "Palau", "given": "Anna", "initials": "A"}, {"family": "Dong", "given": "Wenbo", "initials": "W", "orcid": "0000-0002-5209-4884", "researcher": {"href": "https://publications.scilifelab.se/researcher/81bd1bba109e48ab9e3c19d3c947bf82.json"}}, {"family": "Persson", "given": "Jenna", "initials": "J"}, {"family": "Durand-Dubief", "given": "Micka\u00ebl", "initials": "M", "orcid": "0000-0002-8556-4459", "researcher": {"href": "https://publications.scilifelab.se/researcher/85c11d5d8d94488aad3e77a84b89ff8d.json"}}, {"family": "Svensson", "given": "J Peter", "initials": "JP", "orcid": "0000-0002-5863-6250", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c226ba652024fdabbbf9203e1edb5d1.json"}}, {"family": "Lennartsson", "given": "Andreas", "initials": "A"}], "type": "journal article", "published": "2020-01-10", "journal": {"title": "Epigenetics", "issn": "1559-2308", "volume": "15", "issue": "6-7", "pages": "702-714", "issn-l": "1559-2294"}, "abstract": "The transcriptional program that dictates haematopoietic cell fate and differentiation requires an epigenetic regulatory and memory function, provided by a network of epigenetic factors that regulate DNA methylation, post-translational histone modifications and chromatin structure. Disturbed epigenetic regulation causes perturbations in the blood cell differentiation program that results in various types of haematopoietic disorders. Thus, accurate epigenetic regulation is essential for functional haematopoiesis. In this study, we used a CRISPR-Cas9 screening approach to identify new epigenetic regulators in myeloid differentiation. We designed a Chromatin-UMI CRISPR guide library targeting 1092 epigenetic regulators. Phorbol 12-myristate 13-acetate (PMA) treatment of the chronic myeloid leukaemia cell line K-562 was used as a megakaryocytic myeloid differentiation model. Both previously described developmental epigenetic regulators and novel factors were identified in our screen. In this study, we validated and characterized a role for the chromatin remodeller CHD2 in myeloid proliferation and megakaryocytic differentiation.", "doi": "10.1080/15592294.2019.1710913", "pmid": "31900031", "labels": {"NGI Stockholm (Genomics Production)": "Service", "NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "CRISPR Functional Genomics": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7574388"}], "notes": [], "created": "2020-01-20T10:22:28.949Z", "modified": "2024-01-16T13:48:43.086Z"}, {"entity": "publication", "iuid": "ad8084cfea9d4cbfb73fec4819833186", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ad8084cfea9d4cbfb73fec4819833186.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ad8084cfea9d4cbfb73fec4819833186"}}, "title": "Longitudinal DNA methylation changes at MET may alter HGF/c-MET signalling in adolescents at risk for depression.", "authors": [{"family": "Ciuculete", "given": "Diana M", "initials": "DM", "orcid": "0000-0001-6377-0270", "researcher": {"href": "https://publications.scilifelab.se/researcher/1facf036e83a4fd1934204cc1dc7ee4d.json"}}, {"family": "Voisin", "given": "Sarah", "initials": "S", "orcid": "0000-0002-4074-7083", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c6eab1a09084c1499c442d89bd2ff83.json"}}, {"family": "Kular", "given": "Lara", "initials": "L"}, {"family": "Welihinda", "given": "Nipuni", "initials": "N"}, {"family": "Jonsson", "given": "J\u00f6rgen", "initials": "J"}, {"family": "Jagodic", "given": "Maja", "initials": "M"}, {"family": "Mwinyi", "given": "Jessica", "initials": "J"}, {"family": "Schi\u00f6th", "given": "Helgi B", "initials": "HB"}], "type": "journal article", "published": "2019-12-19", "journal": {"volume": "15", "issn": "1559-2308", "issue": "6-7", "pages": "646-663", "title": "Epigenetics", "issn-l": "1559-2294"}, "abstract": "Unrecognized depression during adolescence can result in adult suicidal behaviour. The aim of this study was to identify, replicate and characterize DNA methylation (DNAm) shifts in depression aetiology, using a longitudinal, multi-tissue (blood and brain) and multi-layered (genetics, epigenetics, transcriptomics) approach. We measured genome-wide blood DNAm data at baseline and one-year follow-up, and imputed genetic variants, in 59 healthy adolescents comprising the discovery cohort. Depression and suicidal symptoms were determined using the Development and Well-Being Assessment (DAWBA) depression band, Montgomery-\u00c5sberg Depression Rating Scale-Self (MADRS-S) and SUicide Assessment Scale (SUAS). DNAm levels at follow-up were regressed against depression scores, adjusting for sex, age and the DNAm residuals at baseline. Higher methylation levels of 5% and 13% at cg24627299 within the MET gene were associated with higher depression scores (praw<1e-4) and susceptibility for suicidal symptoms (padj.<0.005). The nearby rs39748 was discovered to be a methylation and expression quantitative trait locus in blood cells. mRNA levels of hepatocyte growth factor (HGF) expression, known to strongly interact with MET, were inversely associated with methylation levels at cg24627299, in an independent cohort of 1180 CD14+ samples. In an open-access dataset of brain tissue, lower methylation at cg24627299 was found in 45 adults diagnosed with major depressive disorder compared with matched controls (padj.<0.05). Furthermore, lower MET expression was identified in the hippocampus of depressed individuals compared with controls in a fourth, independent cohort. Our findings reveal methylation changes at MET in the pathology of depression, possibly involved in downregulation of HGF/c-MET signalling the hippocampal region.", "doi": "10.1080/15592294.2019.1700628", "pmid": "31852353", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7574381"}], "notes": [], "created": "2020-01-07T14:39:03.531Z", "modified": "2024-01-16T13:48:43.281Z"}, {"entity": "publication", "iuid": "5e70d33879bb4e06877cb055d7c9c062", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5e70d33879bb4e06877cb055d7c9c062.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5e70d33879bb4e06877cb055d7c9c062"}}, "title": "EZH2 upregulates the PI3K/AKT pathway through IGF1R and MYC in clinically aggressive chronic lymphocytic leukaemia.", "authors": [{"family": "Kosalai", "given": "Subazini Thankaswamy", "initials": "ST"}, {"family": "Morsy", "given": "Mohammad Hamdy Abdelrazak", "initials": "MHA"}, {"family": "Papakonstantinou", "given": "Nikos", "initials": "N"}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Stavroyianni", "given": "Niki", "initials": "N"}, {"family": "Kanduri", "given": "Chandrasekhar", "initials": "C"}, {"family": "Stamatopoulos", "given": "Kostas", "initials": "K"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}, {"family": "Kanduri", "given": "Meena", "initials": "M"}], "type": "journal article", "published": "2019-11-00", "journal": {"volume": "14", "issn": "1559-2308", "issue": "11", "pages": "1125-1140", "title": "Epigenetics", "issn-l": "1559-2294"}, "abstract": "EZH2 is overexpressed in poor-prognostic chronic lymphocytic leukaemia (CLL) cases, acting as an oncogene; however, thus far, the EZH2 target genes in CLL have not been disclosed. In this study, using ChIP-sequencing, we identified EZH2 and H3K27me3 target genes in two prognostic subgroups of CLL with distinct prognosis and outcome, i.e., cases with unmutated (U-CLL, n = 6) or mutated IGHV genes (M-CLL, n = 6). While the majority of oncogenic pathways were equally enriched for EZH2 target genes in both prognostic subgroups, PI3K pathway genes were differentially bound by EZH2 in U-CLL versus M-CLL. The occupancy of EZH2 for selected PI3K pathway target genes was validated in additional CLL samples (n = 16) and CLL cell lines using siRNA-mediated EZH2 downregulation and ChIP assays. Intriguingly, we found that EZH2 directly binds to the IGF1R promoter along with MYC and upregulates IGF1R expression in U-CLL, leading to downstream PI3K activation. By investigating an independent CLL cohort (n = 96), a positive correlation was observed between EZH2 and IGF1R expression with higher levels in U-CLL compared to M-CLL. Accordingly, siRNA-mediated downregulation of either EZH2, MYC or IGF1R and treatment with EZH2 and MYC pharmacological inhibitors in the HG3 CLL cell line induced a significant reduction in PI3K pathway activation. In conclusion, we characterize for the first time EZH2 target genes in CLL revealing a hitherto unknown implication of EZH2 in modulating the PI3K pathway in a non-canonical, PRC2-independent way, with potential therapeutic implications considering that PI3K inhibitors are effective therapeutic agents for CLL.", "doi": "10.1080/15592294.2019.1633867", "pmid": "31216925", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6773411"}], "notes": [], "created": "2019-12-03T10:47:45.011Z", "modified": "2024-01-16T13:48:43.618Z"}, {"entity": "publication", "iuid": "d5672f9c78a34140873fcaa57aaafb89", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d5672f9c78a34140873fcaa57aaafb89.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d5672f9c78a34140873fcaa57aaafb89"}}, "title": "Hypermethylation-associated downregulation of microRNA-4456 in hypersexual disorder with putative influence on oxytocin signalling: A DNA methylation analysis of miRNA genes.", "authors": [{"family": "Bostr\u00f6m", "given": "Adrian E", "initials": "AE"}, {"family": "Chatzittofis", "given": "Andreas", "initials": "A"}, {"family": "Ciuculete", "given": "Diana-Maria", "initials": "DM"}, {"family": "Flanagan", "given": "John N", "initials": "JN"}, {"family": "Krattinger", "given": "Regina", "initials": "R"}, {"family": "Bandstein", "given": "Marcus", "initials": "M"}, {"family": "Mwinyi", "given": "Jessica", "initials": "J"}, {"family": "Kullak-Ublick", "given": "Gerd A", "initials": "GA"}, {"family": "\u00d6berg", "given": "Katarina G\u00f6rts", "initials": "KG"}, {"family": "Arver", "given": "Stefan", "initials": "S"}, {"family": "Schi\u00f6th", "given": "Helgi B", "initials": "HB"}, {"family": "Jokinen", "given": "Jussi", "initials": "J"}], "type": "journal article", "published": "2019-09-22", "journal": {"volume": null, "issn": "1559-2308", "issue": null, "pages": "1-16", "title": "Epigenetics", "issn-l": "1559-2294"}, "abstract": "Hypersexual disorder (HD) was proposed as a diagnosis in the DSM-5 and the classification 'Compulsive Sexual Behavior Disorder' is now presented as an impulse-control disorder in ICD-11. HD incorporates several pathophysiological mechanisms; including impulsivity, compulsivity, sexual desire dysregulation and sexual addiction. No previous study investigated HD in a methylation analysis limited to microRNA (miRNA) associated CpG-sites. The genome wide methylation pattern was measured in whole blood from 60 subjects with HD and 33 healthy volunteers using the Illumina EPIC BeadChip. 8,852 miRNA associated CpG-sites were investigated in multiple linear regression analyses of methylation M-values to a binary independent variable of disease state (HD or healthy volunteer), adjusting for optimally determined covariates. Expression levels of candidate miRNAs were investigated in the same individuals for differential expression analysis. Candidate methylation loci were further studied for an association with alcohol dependence in an independent cohort of 107 subjects. Two CpG-sites were borderline significant in HD - cg18222192 (MIR708)(\n            p < 10E-05,pFDR = 5.81E-02) and cg01299774 (MIR4456)(p < 10E-06, pFDR = 5.81E-02). MIR4456 was significantly lower expressed in HD in both univariate (p < 0.0001) and multivariate (p < 0.05) analyses. Cg01299774 methylation levels were inversely correlated with expression levels of MIR4456 (p < 0.01) and were also differentially methylated in alcohol dependence (p = 0.026). Gene target prediction and pathway analysis revealed that MIR4456 putatively targets genes preferentially expressed in brain and that are involved in major neuronal molecular mechanisms thought to be relevant for HD, e.g., the oxytocin signalling pathway. In summary, our study implicates a potential contribution of MIR4456 in the pathophysiology of HD by putatively influencing oxytocin signalling.", "doi": "10.1080/15592294.2019.1656157", "pmid": "31542994", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2019-09-26T06:48:24.191Z", "modified": "2024-01-16T13:48:43.861Z"}, {"entity": "publication", "iuid": "93379f5a15c7458fac70fdb76edbaee8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/93379f5a15c7458fac70fdb76edbaee8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/93379f5a15c7458fac70fdb76edbaee8"}}, "title": "Mutation dynamics of CpG dinucleotides during a recent event of vertebrate diversification.", "authors": [{"family": "P\u00e9rtille", "given": "F\u00e1bio", "initials": "F", "orcid": "0000-0002-7214-9184", "researcher": {"href": "https://publications.scilifelab.se/researcher/2279c5ebf16f419bab7c3af87bac81d3.json"}}, {"family": "Da Silva", "given": "Vinicius H", "initials": "VH"}, {"family": "Johansson", "given": "Anna M", "initials": "AM", "orcid": "0000-0002-9762-0497", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbd1ea80ec964bc3ab675e84b27d17e6.json"}}, {"family": "Lindstr\u00f6m", "given": "Tom", "initials": "T", "orcid": "0000-0001-7856-2925", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a619b495eed4a41a65f2bc7a3c7c5dc.json"}}, {"family": "Wright", "given": "Dominic", "initials": "D"}, {"family": "Coutinho", "given": "Luiz L", "initials": "LL"}, {"family": "Jensen", "given": "Per", "initials": "P"}, {"family": "Guerrero-Bosagna", "given": "Carlos", "initials": "C", "orcid": "0000-0003-1935-5875", "researcher": {"href": "https://publications.scilifelab.se/researcher/0175a0da7ca147d4a0430b085ed23669.json"}}], "type": "journal article", "published": "2019-07-00", "journal": {"volume": "14", "issn": "1559-2308", "issue": "7", "pages": "685-707", "title": "Epigenetics", "issn-l": "1559-2294"}, "abstract": "DNA methylation in CpGs dinucleotides is associated with high mutability and disappearance of CpG sites during evolution. Although the high mutability of CpGs is thought to be relevant for vertebrate evolution, very little is known on the role of CpG-related mutations in the genomic diversification of vertebrates. Our study analysed genetic differences in chickens, between Red Junglefowl (RJF; the living closest relative to the ancestor of domesticated chickens) and domesticated breeds, to identify genomic dynamics that have occurred during the process of their domestication, focusing particularly on CpG-related mutations. Single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) between RJF and these domesticated breeds were assessed in a reduced fraction of their genome. Additionally, DNA methylation in the same fraction of the genome was measured in the sperm of RJF individuals to identify possible correlations with the mutations found between RJF and the domesticated breeds. Our study shows that although the vast majority of CpG-related mutations found relate to CNVs, CpGs disproportionally associate to SNPs in comparison to CNVs, where they are indeed substantially under-represented. Moreover, CpGs seem to be hotspots of mutations related to speciation. We suggest that, on the one hand, CpG-related mutations in CNV regions would promote genomic 'flexibility' in evolution, i.e., the ability of the genome to expand its functional possibilities; on the other hand, CpG-related mutations in SNPs would relate to genomic 'specificity' in evolution, thus, representing mutations that would associate with phenotypic traits relevant for speciation.", "doi": "10.1080/15592294.2019.1609868", "pmid": "31070073", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6557589"}], "notes": [], "created": "2020-01-08T12:39:10.372Z", "modified": "2021-06-18T14:18:18.038Z"}, {"entity": "publication", "iuid": "8152d181864c494abdbe3a682fce8e68", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8152d181864c494abdbe3a682fce8e68.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8152d181864c494abdbe3a682fce8e68"}}, "title": "Identification of DNA methylation patterns predisposing for an efficient response to BCG vaccination in healthy BCG-na\u00efve subjects.", "authors": [{"family": "Das", "given": "Jyotirmoy", "initials": "J"}, {"family": "Verma", "given": "Deepti", "initials": "D"}, {"family": "Gustafsson", "given": "Mika", "initials": "M"}, {"family": "Lerm", "given": "Maria", "initials": "M"}], "type": "journal article", "published": "2019-06-00", "journal": {"volume": "14", "issn": "1559-2308", "issue": "6", "pages": "589-601", "title": "Epigenetics", "issn-l": "1559-2294"}, "abstract": "The protection against tuberculosis induced by the Bacille Calmette Gu\u00e9rin (BCG) vaccine is unpredictable. In our previous study, altered DNA methylation pattern in peripheral blood mononuclear cells (PBMCs) in response to BCG was observed in a subgroup of individuals, whose macrophages killed mycobacteria effectively ('responders'). These macrophages also showed production of Interleukin-1\u03b2 (IL-1\u03b2) in response to mycobacterial stimuli before vaccination. Here, we hypothesized that the propensity to respond to the BCG vaccine is reflected in the DNA methylome. We mapped the differentially methylated genes (DMGs) in PBMCs isolated from responders/non-responders at the time point before vaccination aiming to identify possible predictors of BCG responsiveness. We identified 43 DMGs and subsequent bioinformatic analyses showed that these were enriched for actin-modulating pathways, predicting differences in phagocytosis. This could be validated by experiments showing that phagocytosis of mycobacteria, which is an event preceding mycobacteria-induced IL-1\u03b2 production, was strongly correlated with the DMG pattern.", "doi": "10.1080/15592294.2019.1603963", "pmid": "31010371", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6557603"}], "notes": [], "created": "2019-09-16T11:35:20.505Z", "modified": "2024-01-16T13:48:44.266Z"}, {"entity": "publication", "iuid": "e76ed1b2f4ea42628c05f389e376f495", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e76ed1b2f4ea42628c05f389e376f495.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e76ed1b2f4ea42628c05f389e376f495"}}, "title": "Epigenetic influences on aging: a longitudinal genome-wide methylation study in old Swedish twins", "authors": [{"family": "Wang", "given": "Yunzhang", "initials": "Y"}, {"family": "Karlsson", "given": "Robert", "initials": "R"}, {"family": "Lampa", "given": "Erik", "initials": "E"}, {"family": "Zhang", "given": "Qian", "initials": "Q"}, {"family": "Hedman", "given": "\u00c5sa K", "initials": "\u00c5K"}, {"family": "Almgren", "given": "Malin", "initials": "M"}, {"family": "Almqvist", "given": "Catarina", "initials": "C"}, {"family": "McRae", "given": "Allan F", "initials": "AF"}, {"family": "Marioni", "given": "Riccardo E", "initials": "RE"}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "Visscher", "given": "Peter M", "initials": "PM"}, {"family": "Deary", "given": "Ian J", "initials": "IJ"}, {"family": "Lind", "given": "Lars", "initials": "L"}, {"family": "Morris", "given": "Tiffany", "initials": "T"}, {"family": "Beck", "given": "Stephan", "initials": "S"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S"}], "type": "journal-article", "published": "2018-09-28", "journal": {"volume": null, "issn": "1559-2308", "issue": null, "pages": null, "title": "Epigenetics", "issn-l": "1559-2294"}, "abstract": null, "doi": "10.1080/15592294.2018.1526028", "pmid": "30264654", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "EBI", "description": "https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-7309", "key": "E-MTAB-7309"}], "notes": [], "created": "2018-10-03T12:19:07.045Z", "modified": "2024-01-16T13:48:45.464Z"}, {"entity": "publication", "iuid": "795978f5e49e4146bc9e7b6c2a0f4e67", "links": {"self": {"href": "https://publications.scilifelab.se/publication/795978f5e49e4146bc9e7b6c2a0f4e67.json"}, "display": {"href": "https://publications.scilifelab.se/publication/795978f5e49e4146bc9e7b6c2a0f4e67"}}, "title": "Epigenetic changes as prognostic predictors in endometrial carcinomas.", "authors": [{"family": "Farkas", "given": "Sanja A", "initials": "SA"}, {"family": "Sorbe", "given": "Bengt G", "initials": "BG"}, {"family": "Nilsson", "given": "Torbj\u00f6rn K", "initials": "TK"}], "type": "journal article", "published": "2017-01-02", "journal": {"volume": "12", "issn": "1559-2308", "issue": "1", "pages": "19-26", "title": "Epigenetics", "issn-l": "1559-2294"}, "abstract": "Endometrial carcinoma is one of the most frequent gynecological malignancies of the female. The diagnostic and prognostic markers for the high-risk subgroups with unfavorable prognosis are under intense debate worldwide, and, therefore, the aim of this study was to identify new potential DNA methylation markers for the high-risk groups. We used the Illumina Infinium HumanMethylation450 BeadChip to analyze the DNA methylation pattern and investigated its association with clinicopathological features important for defining the high-risk (FIGO-grade 3) and low-risk (FIGO-grade 1) groups of patients with endometrial cancer (n = 31 and n = 39, respectively). We identified specific DNA methylation signature in high-risk endometrial tumors, and potential molecular biomarker genes (TBX2, CHST11, and NID2) associated with unfavorable clinical predictive and prognostic factors.", "doi": "10.1080/15592294.2016.1252891", "pmid": "27874289", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC5270631"}], "notes": [], "created": "2017-05-03T13:01:43.385Z", "modified": "2020-01-21T13:56:03.152Z"}, {"entity": "publication", "iuid": "0f760d33880c40d7a49894a781e53fbc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0f760d33880c40d7a49894a781e53fbc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0f760d33880c40d7a49894a781e53fbc"}}, "title": "Rapid and specific hypomethylation of enhancers in endothelial cells during adaptation to cell culturing.", "authors": [{"family": "Magnusson", "given": "Mia", "initials": "M"}, {"family": "Larsson", "given": "Pia", "initials": "P"}, {"family": "Lu", "given": "Emma Xuchun", "initials": "EX"}, {"family": "Bergh", "given": "Niklas", "initials": "N"}, {"family": "Car\u00e9n", "given": "Helena", "initials": "H"}, {"family": "Jern", "given": "Sverker", "initials": "S"}], "type": "journal article", "published": "2016-08-02", "journal": {"volume": "11", "issn": "1559-2308", "issue": "8", "pages": "614-624", "title": "Epigenetics", "issn-l": "1559-2294"}, "abstract": "Epigenetics, including DNA methylation, is one way for a cell to respond to the surrounding environment. Traditionally, DNA methylation has been perceived as a quite stable modification; however, lately, there have been reports of a more dynamic CpG methylation that can be affected by, for example, long-term culturing. We recently reported that methylation in the enhancer of the gene encoding the key fibrinolytic enzyme tissue-type plasminogen activator (t-PA) was rapidly erased during cell culturing. In the present study we used sub-culturing of human umbilical vein endothelial cells (HUVECs) as a model of environmental challenge to examine how fast genome-wide methylation changes can arise. To assess genome-wide DNA methylation, the Infinium HumanMethylation450 BeadChip was used on primary, passage 0, and passage 4 HUVECs. Almost 2% of the analyzed sites changed methylation status to passage 4, predominantly displaying hypomethylation. Sites annotated as enhancers were overrepresented among the differentially methylated sites (DMSs). We further showed that half of the corresponding genes concomitantly altered their expression, most of them increasing in expression. Interestingly, the stroke-related gene HDAC9 increased its expression several hundredfold. This study reveals a rapid hypomethylation of CpG sites in enhancer elements during the early stages of cell culturing. As many methods for methylation analysis are biased toward CpG rich promoter regions, we suggest that such methods may not always be appropriate for the study of methylation dynamics. In addition, we found that significant changes in expression arose in genes with enhancer DMSs. HDAC9 displayed the most prominent increase in expression, indicating, for the first time, that dynamic enhancer methylation may be central in regulating this important stroke-associated gene.", "doi": "10.1080/15592294.2016.1192734", "pmid": "27302749", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC4990226"}], "notes": [], "created": "2017-05-03T13:01:43.087Z", "modified": "2021-07-08T12:41:32.066Z"}, {"entity": "publication", "iuid": "126c6aa0c64948e29dfe5d96fb13062c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/126c6aa0c64948e29dfe5d96fb13062c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/126c6aa0c64948e29dfe5d96fb13062c"}}, "title": "Epigenetic silencing of miR-26A1 in chronic lymphocytic leukemia and mantle cell lymphoma: Impact on EZH2 expression.", "authors": [{"family": "Kopparapu", "given": "Pradeep Kumar", "initials": "PK"}, {"family": "Bhoi", "given": "Sujata", "initials": "S"}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Arabanian", "given": "Laleh S", "initials": "LS"}, {"family": "Plevova", "given": "Karla", "initials": "K"}, {"family": "Pospisilova", "given": "Sarka", "initials": "S"}, {"family": "Wasik", "given": "Agata M", "initials": "AM"}, {"family": "Croci", "given": "Giorgio Alberto", "initials": "GA"}, {"family": "Sander", "given": "Birgitta", "initials": "B"}, {"family": "Paulli", "given": "Marco", "initials": "M"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}, {"family": "Kanduri", "given": "Meena", "initials": "M"}], "type": "journal article", "published": "2016-05-03", "journal": {"volume": "11", "issn": "1559-2308", "issue": "5", "pages": "335-343", "title": "Epigenetics", "issn-l": "1559-2294"}, "abstract": "Downregulation of miR26A1 has been reported in various B-cell malignancies; however, the mechanism behind its deregulation remains largely unknown. We investigated miR26A1 methylation and expression levels in a well-characterized series of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). From 450K methylation arrays, we first observed miR26A1 (cg26054057) as uniformly hypermethylated in MCL (n = 24) (all >75%), while CLL (n = 18) showed differential methylation between prognostic subgroups. Extended analysis using pyrosequencing confirmed our findings and real-time quantitative PCR verified low miR26A1 expression in both CLL (n = 70) and MCL (n = 38) compared to normal B-cells. Notably, the level of miR26A1 methylation predicted outcome in CLL, with higher levels seen in poor-prognostic, IGHV-unmutated CLL. Since EZH2 was recently reported as a target for miR26A1, we analyzed the expression levels of both miR26A1 and EZH2 in primary CLL samples and observed an inverse correlation. By overexpression of miR26A1 in CLL and MCL cell lines, reduced EZH2 protein levels were observed using both Western blot and flow cytometry. In contrast, methyl-inhibitor treatment led to upregulated miR26A1 expression with a parallel decrease of EZH2 expression. Finally, increased levels of apoptosis were observed in miR26A1-overexpressing cell lines, further underscoring the functional relevance of miR26A1. In summary, we propose that epigenetic silencing of miR26A1 is required for the maintenance of increased levels of EZH2, which in turn translate into a worse outcome, as shown in CLL, highlighting miR26A1 as a tumor suppressor miRNA.", "doi": "10.1080/15592294.2016.1164375", "pmid": "27052808", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC4889270"}], "notes": [], "created": "2017-05-03T13:00:05.081Z", "modified": "2024-01-16T13:48:50.114Z"}, {"entity": "publication", "iuid": "12195c4c6b864b1ebfd2412dab017656", "links": {"self": {"href": "https://publications.scilifelab.se/publication/12195c4c6b864b1ebfd2412dab017656.json"}, "display": {"href": "https://publications.scilifelab.se/publication/12195c4c6b864b1ebfd2412dab017656"}}, "title": "Differential methylation in CN-AML preferentially targets non-CGI regions and is dictated by DNMT3A mutational status and associated with predominant hypomethylation of HOX genes.", "authors": [{"family": "Qu", "given": "Ying", "initials": "Y"}, {"family": "Lennartsson", "given": "Andreas", "initials": "A"}, {"family": "Gaidzik", "given": "Verena I", "initials": "VI"}, {"family": "Deneberg", "given": "Stefan", "initials": "S"}, {"family": "Karimi", "given": "Mohsen", "initials": "M"}, {"family": "Bengtz\u00e9n", "given": "Sofia", "initials": "S"}, {"family": "H\u00f6glund", "given": "Martin", "initials": "M"}, {"family": "Bullinger", "given": "Lars", "initials": "L"}, {"family": "D\u00f6hner", "given": "Konstanze", "initials": "K"}, {"family": "Lehmann", "given": "S\u00f6ren", "initials": "S"}], "type": "journal article", "published": "2014-08-00", "journal": {"volume": "9", "issn": "1559-2308", "issue": "8", "pages": "1108-1119", "title": "Epigenetics", "issn-l": "1559-2294"}, "abstract": "The extent and role of aberrant DNA methylation in promoter CpG islands (CGIs) have been extensively studied in leukemia and other malignancies. Still, CGIs represent only a small fraction of the methylome. We aimed to characterize genome-wide differential methylation of cytogenetically normal AML (CN-AML) cells compared with normal CD34(+) bone marrow cells using the Illumina 450K methylation array. Differential methylation in CN-AML was most prominent in genomic areas far from CGIs, in so called open sea regions. Furthermore, differential methylation was specifically found in genes encoding transcription factors (TFs), with WT1 being the most differentially methylated TF. Among genetic mutations in AML, DNMT3A mutations showed the most prominent association with the DNA methylation pattern, characterized by hypomethylation of CGIs (as compared with DNMT3A wild type cases). The differential methylation in DNMT3A mutant cells vs. wild type cells was predominantly found in HOX genes, which were hypomethylated. These results were confirmed and validated in an independent CN-AML cohort. In conclusion, we show that, in CN-AML, the most pronounced changes in DNA methylation occur in non-CGI regions and that DNMT3A mutations confer a pattern of global hypomethylation that specifically targets HOX genes.", "doi": "10.4161/epi.29315", "pmid": "24866170", "labels": {"National Genomics Infrastructure": null, "Bioinformatics and Expression Analysis (BEA)": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "29315"}, {"db": "pmc", "key": "PMC4164496"}], "notes": [], "created": "2017-05-04T14:58:32.663Z", "modified": "2020-01-21T13:56:00.788Z"}, {"entity": "publication", "iuid": "a2b9b87ef49745668774781bc51b9314", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a2b9b87ef49745668774781bc51b9314.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a2b9b87ef49745668774781bc51b9314"}}, "title": "microRNA-34b/c on chromosome 11q23 is aberrantly methylated in chronic lymphocytic leukemia.", "authors": [{"family": "Deneberg", "given": "Stefan", "initials": "S"}, {"family": "Kanduri", "given": "Meena", "initials": "M"}, {"family": "Ali", "given": "Dina", "initials": "D"}, {"family": "Bengtzen", "given": "Sofia", "initials": "S"}, {"family": "Karimi", "given": "Mohsen", "initials": "M"}, {"family": "Qu", "given": "Ying", "initials": "Y"}, {"family": "Kimby", "given": "Eva", "initials": "E"}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}, {"family": "Lennartsson", "given": "Andreas", "initials": "A"}, {"family": "Lehmann", "given": "S\u00f6ren", "initials": "S"}], "type": "journal article", "published": "2014-06-00", "journal": {"volume": "9", "issn": "1559-2308", "issue": "6", "pages": "910-917", "title": "Epigenetics", "issn-l": "1559-2294"}, "abstract": "A commonly deleted region in chronic lymphocytic leukemia (CLL) is the 11q22-23 region, which encompasses the ATM gene. Evidence suggests that tumor suppressor genes other than ATM are likely to be involved in CLL with del(11q). A microRNA (miR) cluster including the miR-34b and miR-34c genes is located, among other genes, within the commonly deleted region (CDR) at 11q. Interestingly, these miRs are part of the TP53 network and have been shown to be epigenetically regulated. In this study, we investigated the expression and methylation status of these miRs in a well-characterized cohort of CLL, including cases with/without 11q-deletion. We show that the miR-34b/c promoter was aberrantly hypermethylated in a large proportion of CLL cases (48%, 25/52 cases). miR-34b/c expression correlated inversely to DNA methylation (P = 0.003), and presence of high H3K37me3 further suppressed expression regardless of methylation status. Furthermore, increased miR-34b/c methylation inversely correlated with the presence of 11q-deletion, indicating that methylation and del(11q) independently silence these miRs. Finally, 5-azacytidine and trichostatin A exposure synergistically increased the expression of miR-34b/c in CLL cells, and transfection of miR-34b or miR-34c into HG3 CLL cells significantly increased apoptosis. Altogether, our novel data suggest that miR-34b/c is a candidate tumor suppressor that is epigenetically silenced in CLL.", "doi": "10.4161/epi.28603", "pmid": "24686393", "labels": {"National Genomics Infrastructure": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "28603"}, {"db": "pmc", "key": "PMC4053441"}], "notes": [], "created": "2017-05-04T14:58:32.363Z", "modified": "2020-01-21T13:56:04.188Z"}, {"entity": "publication", "iuid": "29c8265f35684c9b9aa061f8bba87c57", "links": {"self": {"href": "https://publications.scilifelab.se/publication/29c8265f35684c9b9aa061f8bba87c57.json"}, "display": {"href": "https://publications.scilifelab.se/publication/29c8265f35684c9b9aa061f8bba87c57"}}, "title": "Genome-wide DNA methylation assay reveals novel candidate biomarker genes in cervical cancer.", "authors": [{"family": "Farkas", "given": "Sanja A", "initials": "SA"}, {"family": "Milutin-Ga\u0161perov", "given": "Nina", "initials": "N"}, {"family": "Grce", "given": "Magdalena", "initials": "M"}, {"family": "Nilsson", "given": "Torbj\u00f6rn K", "initials": "TK"}], "type": "journal article", "published": "2013-11-00", "journal": {"volume": "8", "issn": "1559-2308", "issue": "11", "pages": "1213-1225", "title": "Epigenetics", "issn-l": "1559-2294"}, "abstract": "The oncogenic human papilloma viruses (HPVs) are associated with precancerous cervical lesions and development of cervical cancer. The DNA methylation signatures of the host genome in normal, precancerous and cervical cancer tissue may indicate tissue-specific perturbation in carcinogenesis. The aim of this study was to identify new candidate genes that are differentially methylated in squamous cell carcinoma compared with DNA samples from cervical intraepithelial neoplasia grade 3 (CIN3) and normal cervical scrapes. The Illumina Infinium HumanMethylation450 BeadChip method identifies genome-wide DNA methylation changes in CpG islands, CpG shores and shelves. Our findings showed an extensive differential methylation signature in cervical cancer compared with the CIN3 or normal cervical tissues. The identified candidate biomarker genes for cervical cancer represent several types of mechanisms in the cellular machinery that are epigenetically deregulated by hypermethylation, such as membrane receptors, intracellular signaling and gene transcription. The results also confirm extensive hypomethylation of genes in the immune system in cancer tissues. These insights into the functional role of DNA methylome alterations in cervical cancer could be clinically applicable in diagnostics and prognostics, and may guide the development of new epigenetic therapies.", "doi": "10.4161/epi.26346", "pmid": "24030264", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "pii", "key": "26346"}], "notes": [], "created": "2017-05-04T15:01:17.049Z", "modified": "2020-01-21T13:56:01.204Z"}, {"entity": "publication", "iuid": "b5717e1da4704310b8977f7958d2bf33", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b5717e1da4704310b8977f7958d2bf33.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b5717e1da4704310b8977f7958d2bf33"}}, "title": "Distinct transcriptional control in major immunogenetic subsets of chronic lymphocytic leukemia exhibiting subset-biased global DNA methylation profiles.", "authors": [{"family": "Kanduri", "given": "Meena", "initials": "M"}, {"family": "Marincevic", "given": "Millaray", "initials": "M"}, {"family": "Halld\u00f3rsd\u00f3ttir", "given": "Anna M", "initials": "AM"}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Junevik", "given": "Katarina", "initials": "K"}, {"family": "Ntoufa", "given": "Stavroula", "initials": "S"}, {"family": "Kultima", "given": "Hanna G\u00f6ransson", "initials": "HG"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Juliusson", "given": "Gunnar", "initials": "G"}, {"family": "Andersson", "given": "Per-Ola", "initials": "PO"}, {"family": "Ehrencrona", "given": "Hans", "initials": "H"}, {"family": "Stamatopoulos", "given": "Kostas", "initials": "K"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}], "type": "journal article", "published": "2012-12-01", "journal": {"volume": "7", "issn": "1559-2308", "issue": "12", "pages": "1435-1442", "title": "Epigenetics", "issn-l": "1559-2294"}, "abstract": "Chronic lymphocytic leukemia (CLL) can be divided into prognostic subgroups based on the IGHV gene mutational status, and is further characterized by multiple subsets of cases with quasi-identical or stereotyped B cell receptors that also share clinical and biological features. We recently reported differential DNA methylation profiles in IGHV-mutated and IGHV-unmutated CLL subgroups. For the first time, we here explore the global methylation profiles of stereotyped subsets with different prognosis, by applying high-resolution methylation arrays on CLL samples from three major stereotyped subsets: the poor-prognostic subsets #1 (n = 15) and #2 (n = 9) and the favorable-prognostic subset #4 (n = 15). Overall, the three subsets exhibited significantly different methylation profiles, which only partially overlapped with those observed in our previous study according to IGHV gene mutational status. Specifically, gene ontology analysis of the differentially methylated genes revealed a clear enrichment of genes involved in immune response, such as B cell activation (e.g., CD80, CD86 and IL10), with higher methylation levels in subset #1 than subsets #2 and #4. Accordingly, higher expression of the co-stimulatory molecules CD80 and CD86 was demonstrated in subset #4 vs. subset #1, pointing to a key role for these molecules in the crosstalk of CLL subset #4 cells with the microenvironment. In summary, investigation of three prototypic, stereotyped CLL subsets revealed distinct DNA methylation profiles for each subset, which suggests subset-biased patterns of transcriptional control and highlights a key role for epigenetics during leukemogenesis.", "doi": "10.4161/epi.22901", "pmid": "23154584", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "22901"}, {"db": "pmc", "key": "PMC3528698"}], "notes": [], "created": "2017-05-04T15:02:56.986Z", "modified": "2017-05-30T12:37:03.981Z"}], "created": "2017-05-09T09:12:19.485Z", "modified": "2020-11-27T13:14:05.578Z"}