TRIM28 modulates nuclear receptor signaling to regulate uterine function

• Published in: Nature communications Vol. 14; no. 1; p. 4605
• Main Authors: Li, Rong, Wang, Tianyuan, Marquardt, Ryan M, Lydon, John P, Wu, San-Pin, DeMayo, Francesco J
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.08.2023; Nature Publishing Group UK; Nature Portfolio
• Subjects: Ablation; Chromatin; Composition; Endometrium; Epithelial cells; Epithelium; Epithelium - metabolism; Estradiol - metabolism; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; Estrogen receptors; Estrogens; Female; Fertility; Humans; Immunoprecipitation; Mass spectrometry; Mass spectroscopy; Pericytes; Pregnancy; Progenitor cells; Progesterone; Progesterone - metabolism; Receptor mechanisms; Receptors; Receptors, Progesterone - genetics; Receptors, Progesterone - metabolism; Rime; Stroma; Tripartite Motif-Containing Protein 28 - genetics; Tripartite Motif-Containing Protein 28 - metabolism; Uterus; Uterus - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-40395-7

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.