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TRIM28 modulates nuclear receptor signaling to regulate uterine function

Author

Listed:
  • Rong Li

    (National Institute of Environmental Health Sciences)

  • Tianyuan Wang

    (National Institute of Environmental Health Sciences)

  • Ryan M. Marquardt

    (National Institute of Environmental Health Sciences)

  • John P. Lydon

    (Baylor College of Medicine)

  • San-Pin Wu

    (National Institute of Environmental Health Sciences)

  • Francesco J. DeMayo

    (National Institute of Environmental Health Sciences)

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.

Suggested Citation

  • Rong Li & Tianyuan Wang & Ryan M. Marquardt & John P. Lydon & San-Pin Wu & Francesco J. DeMayo, 2023. "TRIM28 modulates nuclear receptor signaling to regulate uterine function," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40395-7
    DOI: 10.1038/s41467-023-40395-7
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    1. Simon T. Bond & Emily J. King & Darren C. Henstridge & Adrian Tran & Sarah C. Moody & Christine Yang & Yingying Liu & Natalie A. Mellett & Artika P. Nath & Michael Inouye & Elizabeth J. Tarling & Thom, 2021. "Deletion of Trim28 in committed adipocytes promotes obesity but preserves glucose tolerance," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. Xiaoqiu Wang & Xilong Li & Tianyuan Wang & San-Pin Wu & Jae-Wook Jeong & Tae Hoon Kim & Steven L. Young & Bruce A. Lessey & Rainer B. Lanz & John P. Lydon & Francesco J. DeMayo, 2018. "SOX17 regulates uterine epithelial–stromal cross-talk acting via a distal enhancer upstream of Ihh," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
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    1. Sangappa B. Chadchan & Pooja Popli & Zian Liao & Eryk Andreas & Michelle Dias & Tianyuan Wang & Stephanie J. Gunderson & Patricia T. Jimenez & Denise G. Lanza & Rainer B. Lanz & Charles E. Foulds & Di, 2024. "A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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