The Estrogen Receptor α Cistrome in Human Endometrium and Epithelial Organoids

Sylvia C. Hewitt, San‐Pin Wu, Tianyuan Wang, Madhumita Ray, Ray M, Brolinson M, Steven L. Young, Thomas E Spencer, Alan H. DeCherney, Francesco J. DeMayo
Endocrinology · 2022 · vol. 163(9) · doi:10.1210/endocr/bqac116 · PMID:35895287 · PMC9368022
Lab / animal OA: closed Public-Domain
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This study integrated estrogen receptor α (ESR1) cistromes and transcriptomes from human endometrium and epithelial organoids to identify candidate ESR1 target genes and their associated cellular processes.

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Abstract

Endometrial health is affected by molecular processes that underlie estrogen responses. We assessed estrogen regulation of endometrial function by integrating the estrogen receptor α (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-specific 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.

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MeSH descriptors

Estrogen Receptor alpha Estrogen Receptor alpha Organoids Organoids Chromatin Chromatin Chromatin Endometrium Endometrium Estrogens Estrogens Female Humans Menstrual Cycle Menstrual Cycle

Funding

funders
[{'doi': None, 'name': 'Intramural Research Program', 'awards': []}, {'doi': '10.13039/100000002', 'name': 'National Institutes of Health', 'awards': ['Z1AES103311-01']}, {'doi': '10.13039/100000002', 'name': 'National Institutes of Health', 'awards': ['Z1AHD008926']}, {'doi': '10.13039/100000002', 'name': 'National Institutes of Health', 'awards': ['P01 HD106485']}, {'doi': '10.13039/100000002', 'name': 'National Institutes of Health', 'awards': ['1R01HD096266-04']}]

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References (85)

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License: Public-Domain