Progesterone and glucocorticoid receptors recruit distinct coactivator complexes and promote distinct patterns of

Xiaotao Li1, Jiemin Wong, Sophia Y Tsai

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

Insights

Specific coactivators preferentially bind to steroid receptors, guiding downstream molecular assembly and histone modifications to control gene transcription. This differential recruitment dictates how steroid activation signals are precisely transduced.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Gene Regulation

Background:

  • Steroid receptor function necessitates coactivator interactions.
  • Mechanisms of coactivator complex assembly and signal transduction by steroid receptors are not fully understood.

Purpose of the Study:

  • To investigate the preferential recruitment of coactivators by specific steroid receptors.
  • To elucidate how differential coactivator recruitment influences downstream coregulator assembly and gene transcription.

Main Methods:

  • Utilized a T47D cell line with a mouse mammary tumor virus-chloramphenicol acetyltransferase (MMTV-CAT) reporter.
  • Analyzed coactivator and coregulator recruitment upon ligand treatment for progesterone receptor (PR) and glucocorticoid receptor (GR).
  • Performed loss-of-function experiments to validate the roles of SRC-1 and SRC-2.

Main Results:

  • Progesterone receptor (PR) preferentially recruited SRC-1, leading to CBP recruitment and histone H4 acetylation.
  • Glucocorticoid receptor (GR) preferentially associated with SRC-2 (TIF-2/GRIP-1), recruiting pCAF and modifying histone H3.
  • Loss-of-function studies confirmed SRC-1 and SRC-2 roles in PR- and GR-mediated transcription, respectively.

Conclusions:

  • Specific coactivators are differentially recruited by nuclear receptors.
  • Differential coactivator recruitment dictates the assembly of specific coregulator complexes on target promoters.
  • This process mediates distinct transcription signals for steroid-responsive genes.

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