TRIM28 Modulates Nuclear Receptor Signaling To Regulate Uterine Function

Authors

Rong Li
Tianyuan Wang
Ryan M Marquardt
John P Lydon
San-Pin Wu
Francesco J DeMayo

Publication Date

8-1-2023

Journal

Nature Communications

DOI

10.1038/s41467-023-40395-7

PMID

37528140

PMCID

PMC10393996

PubMedCentral® Posted Date

8-1-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Pregnancy, Female, Humans, Estrogen Receptor alpha, Estradiol, Uterus, Progesterone, Receptors, Progesterone, Epithelium, Tripartite Motif-Containing Protein 28, Reproductive biology, Differentiation, Transcription

Abstract

Estrogen and progesterone, acting through their cognate receptors the estrogen receptor α (ERα) and the progesterone receptor (PR) respectively, regulate uterine biology. Using rapid immunoprecipitation and mass spectrometry (RIME) and co-immunoprecipitation, we identified TRIM28 (Tripartite motif containing 28) as a protein which complexes with ERα and PR in the regulation of uterine function. Impairment of TRIM28 expression results in the inability of the uterus to support early pregnancy through altered PR and ERα action in the uterine epithelium and stroma by suppressing PR and ERα chromatin binding. Furthermore, TRIM28 ablation in PR-expressing uterine cells results in the enrichment of a subset of TRIM28 positive and PR negative pericytes and epithelial cells with progenitor potential. In summary, our study reveals the important roles of TRIM28 in regulating endometrial cell composition and function in women, and also implies its critical functions in other hormone regulated systems.

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