{"entity": "publication", "iuid": "f278321a964942c58d8fad97a3a8e229", "timestamp": "2026-08-12T05:29:27.917Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f278321a964942c58d8fad97a3a8e229.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f278321a964942c58d8fad97a3a8e229"}}, "title": "Ovarian ER\u03b2 cistrome and transcriptome reveal chromatin interaction with LRH-1.", "authors": [{"family": "Birgersson", "given": "Madeleine", "initials": "M"}, {"family": "Indukuri", "given": "Rajitha", "initials": "R"}, {"family": "Lindquist", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Stepanauskaite", "given": "Lina", "initials": "L"}, {"family": "Luo", "given": "Qing", "initials": "Q"}, {"family": "Deng", "given": "Qiaolin", "initials": "Q"}, {"family": "Archer", "given": "Amena", "initials": "A"}, {"family": "Williams", "given": "Cecilia", "initials": "C", "orcid": "0000-0002-0602-2062", "researcher": {"href": "https://publications.scilifelab.se/researcher/89989da8d4e64dd3a30b87fc62ceefae.json"}}], "type": "journal article", "published": "2023-11-29", "journal": {"title": "BMC Biol.", "issn": "1741-7007", "volume": "21", "issue": "1", "pages": "277", "issn-l": "1741-7007"}, "abstract": "Estrogen receptor beta (ER\u03b2, Esr2) plays a pivotal role in folliculogenesis and ovulation, yet its exact mechanism of action is mainly uncharacterized.\n\nWe here performed ER\u03b2 ChIP-sequencing of mouse ovaries followed by complementary RNA-sequencing of wild-type and ER\u03b2 knockout ovaries. By integrating the ER\u03b2 cistrome and transcriptome, we identified its direct target genes and enriched biological functions in the ovary. This demonstrated its strong impact on genes regulating organism development, cell migration, lipid metabolism, response to hypoxia, and response to estrogen. Cell-type deconvolution analysis of the bulk RNA-seq data revealed a decrease in luteal cells and an increased proportion of theca cells and a specific type of cumulus cells upon ER\u03b2 loss. Moreover, we identified a significant overlap with the gene regulatory network of liver receptor homolog 1 (LRH-1, Nr5a2) and showed that ER\u03b2 and LRH-1 extensively bound to the same chromatin locations in granulosa cells. Using ChIP-reChIP, we corroborated simultaneous ER\u03b2 and LRH-1 co-binding at the ER\u03b2-repressed gene Greb1 but not at the ER\u03b2-upregulated genes Cyp11a1 and Fkbp5. Transactivation assay experimentation further showed that ER\u03b2 and LRH-1 can inhibit their respective transcriptional activity at classical response elements.\n\nBy characterizing the genome-wide endogenous ER\u03b2 chromatin binding, gene regulations, and extensive crosstalk between ER\u03b2 and LRH-1, along with experimental corroborations, our data offer genome-wide mechanistic underpinnings of ovarian physiology and fertility.", "doi": "10.1186/s12915-023-01773-1", "pmid": "38031019", "labels": {"NGI Short read": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10688478"}, {"db": "pii", "key": "10.1186/s12915-023-01773-1"}], "notes": [], "created": "2024-01-02T13:30:47.361Z", "modified": "2024-01-16T13:48:31.622Z"}