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The Estrogen Receptor α Cistrome in Human Endometrium and Epithelial Organoids.

Publication ,  Journal Article
Hewitt, SC; Wu, S-P; Wang, T; Ray, M; Brolinson, M; Young, SL; Spencer, TE; DeCherney, A; DeMayo, FJ
Published in: Endocrinology
September 1, 2022

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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Published In

Endocrinology

DOI

EISSN

1945-7170

Publication Date

September 1, 2022

Volume

163

Issue

9

Location

United States

Related Subject Headings

  • Organoids
  • Menstrual Cycle
  • Humans
  • Female
  • Estrogens
  • Estrogen Receptor alpha
  • Endometrium
  • Endocrinology & Metabolism
  • Chromatin
  • 3202 Clinical sciences
 

Citation

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Chicago
ICMJE
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Hewitt, S. C., Wu, S.-P., Wang, T., Ray, M., Brolinson, M., Young, S. L., … DeMayo, F. J. (2022). The Estrogen Receptor α Cistrome in Human Endometrium and Epithelial Organoids. Endocrinology, 163(9). https://doi.org/10.1210/endocr/bqac116
Hewitt, Sylvia C., San-Pin Wu, Tianyuan Wang, Madhumita Ray, Marja Brolinson, Steven L. Young, Thomas E. Spencer, Alan DeCherney, and Francesco J. DeMayo. “The Estrogen Receptor α Cistrome in Human Endometrium and Epithelial Organoids.Endocrinology 163, no. 9 (September 1, 2022). https://doi.org/10.1210/endocr/bqac116.
Hewitt SC, Wu S-P, Wang T, Ray M, Brolinson M, Young SL, et al. The Estrogen Receptor α Cistrome in Human Endometrium and Epithelial Organoids. Endocrinology. 2022 Sep 1;163(9).
Hewitt, Sylvia C., et al. “The Estrogen Receptor α Cistrome in Human Endometrium and Epithelial Organoids.Endocrinology, vol. 163, no. 9, Sept. 2022. Pubmed, doi:10.1210/endocr/bqac116.
Hewitt SC, Wu S-P, Wang T, Ray M, Brolinson M, Young SL, Spencer TE, DeCherney A, DeMayo FJ. The Estrogen Receptor α Cistrome in Human Endometrium and Epithelial Organoids. Endocrinology. 2022 Sep 1;163(9).
Journal cover image

Published In

Endocrinology

DOI

EISSN

1945-7170

Publication Date

September 1, 2022

Volume

163

Issue

9

Location

United States

Related Subject Headings

  • Organoids
  • Menstrual Cycle
  • Humans
  • Female
  • Estrogens
  • Estrogen Receptor alpha
  • Endometrium
  • Endocrinology & Metabolism
  • Chromatin
  • 3202 Clinical sciences