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TRIM28 modulates nuclear receptor signaling to regulate uterine function.

Rong Li1, Tianyuan Wang2, Ryan M Marquardt1

  • 1Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.

Nature Communications
|August 1, 2023
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Summary

Tripartite motif containing 28 (TRIM28) is crucial for supporting early pregnancy by regulating estrogen receptor alpha (ERα) and progesterone receptor (PR) actions in the uterus. TRIM28 deficiency impairs uterine function and alters endometrial cell populations.

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Area of Science:

  • Reproductive biology
  • Molecular endocrinology
  • Cellular and molecular biology

Background:

  • Estrogen and progesterone are key regulators of uterine function via their receptors, ERα and PR.
  • The protein TRIM28's role in uterine biology and its interaction with ERα and PR were previously unknown.

Purpose of the Study:

  • To investigate the role of TRIM28 in regulating uterine function and its interaction with ERα and PR.
  • To determine the impact of TRIM28 deficiency on early pregnancy support and endometrial cell composition.

Main Methods:

  • Rapid immunoprecipitation and mass spectrometry (RIME) to identify protein complexes.
  • Co-immunoprecipitation assays to confirm protein interactions.
  • Analysis of TRIM28's effect on ERα and PR chromatin binding and uterine cell populations.

Main Results:

  • TRIM28 forms complexes with ERα and PR, playing a role in regulating uterine function.
  • Impaired TRIM28 expression disrupts uterine support for early pregnancy by affecting ERα and PR chromatin binding.
  • TRIM28 ablation in uterine cells leads to an enrichment of progenitor cells.

Conclusions:

  • TRIM28 is essential for normal uterine function and early pregnancy support.
  • TRIM28 influences endometrial cell composition and progenitor cell populations.
  • TRIM28 may have critical roles in other hormone-regulated biological systems.