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We assessed estrogen regulation of endometrial function by integrating the estrogen receptor \u03b1 (ESR1) cistromes and transcriptomes of endometrial biopsies taken from the proliferative and mid-secretory phases of the menstrual cycle together with hormonally stimulated endometrial epithelial organoids. The cycle stage\u2013specific ESR1 binding sites were determined by chromatin immunoprecipitation and next-generation sequencing and then integrated with changes in gene expression from RNA sequencing data to infer candidate ESR1 targets in normal endometrium. Genes with ESR1 binding in whole endometrium were enriched for chromatin modification and regulation of cell proliferation. The distribution of ESR1 binding sites in organoids was more distal from gene promoters when compared to primary endometrium and was more similar to the proliferative than the mid-secretory phase ESR1 cistrome. Inferred organoid estrogen\/ESR1 candidate target genes affected formation of cellular protrusions and chromatin modification. Comparison of signaling effected by candidate ESR1 target genes in endometrium vs organoids reveals enrichment of both overlapping and distinct responses. Our analysis of the ESR1 cistromes and transcriptomes from endometrium and organoids provides important resources for understanding how estrogen affects endometrial health and function.<\/jats:p>","DOI":"10.1210\/endocr\/bqac116","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T11:59:23Z","timestamp":1658923163000},"source":"Crossref","is-referenced-by-count":26,"title":["The Estrogen Receptor \u03b1 Cistrome in Human Endometrium and Epithelial Organoids"],"prefix":"10.1210","volume":"163","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7713-0805","authenticated-orcid":false,"given":"Sylvia C","family":"Hewitt","sequence":"first","affiliation":[{"name":"Pregnancy & Female Reproduction, RDBL, NIEHS , Research Triangle Park, North Carolina 27709 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9626-784X","authenticated-orcid":false,"given":"San-pin","family":"Wu","sequence":"additional","affiliation":[{"name":"Pregnancy & Female Reproduction, RDBL, NIEHS , Research Triangle Park, North Carolina 27709 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3970-0771","authenticated-orcid":false,"given":"Tianyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Integrative Bioinformatics Support Group, NIEHS , Research Triangle Park, North Carolina 27709 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhumita","family":"Ray","sequence":"additional","affiliation":[{"name":"Pregnancy & Female Reproduction, RDBL, NIEHS , Research Triangle Park, North Carolina 27709 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8815-3364","authenticated-orcid":false,"given":"Marja","family":"Brolinson","sequence":"additional","affiliation":[{"name":"Program in Reproductive and Adult Endocrinology, NICHD , Bethesda, Maryland 20847 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5205-4495","authenticated-orcid":false,"given":"Steven L","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-766X","authenticated-orcid":false,"given":"Thomas E","family":"Spencer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Women\u2019s Health, University of Missouri , Columbia, Missouri 65211 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4095-1383","authenticated-orcid":false,"given":"Alan","family":"DeCherney","sequence":"additional","affiliation":[{"name":"Program in Reproductive and Adult Endocrinology, NICHD , Bethesda, Maryland 20847 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9480-7336","authenticated-orcid":false,"given":"Francesco J","family":"DeMayo","sequence":"additional","affiliation":[{"name":"Pregnancy & Female Reproduction, RDBL, NIEHS , Research Triangle Park, North Carolina 27709 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2022,7,27]]},"reference":[{"issue":"2-3","key":"2022081112385238600_CIT0001","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s12672-019-0358-9","article-title":"Estrogen signaling in endometrial cancer: a key oncogenic pathway with several open questions","volume":"10","author":"Rodriguez","year":"2019","journal-title":"Horm Cancer."},{"issue":"8","key":"2022081112385238600_CIT0002","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.3390\/ijms21082815","article-title":"Estrogen receptors and endometriosis","volume":"21","author":"Chantalat","year":"2020","journal-title":"Int J Mol Sci."},{"key":"2022081112385238600_CIT0003","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/B978-0-12-397175-3.00024-7","article-title":"Chapter 24 - 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