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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

Synergistic coactivator function by coactivator-associated arginine methyltransferase (CARM) 1 and beta-catenin with

Stephen S Koh1, Hongwei Li, Young-Ho Lee

  • 1Department of Pathology, University of Southern California, Los Angeles, California 90089, USA.

The Journal of Biological Chemistry
|May 2, 2002
PubMed

Insights

This study shows that CARM1 and beta-catenin work together as coactivators for the androgen receptor (AR). Their synergistic action enhances gene transcription, highlighting a new role for CARM1 in AR-mediated signaling.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Epigenetics

Background:

  • The androgen receptor (AR) is a nuclear receptor that regulates gene transcription in response to androgens like dihydrotestosterone.
  • Transcriptional coactivators, including p160 family members, histone acetyltransferase p300, and histone methyltransferase CARM1, are essential for AR-mediated gene activation.
  • Beta-catenin has recently been identified as a coactivator for AR.

Purpose of the Study:

  • To investigate whether CARM1 can cooperate with other coactivator proteins.
  • To determine if CARM1 can function synergistically with beta-catenin and p300 as coactivators for AR.
  • To explore the role of CARM1's methyltransferase activity in its coactivator function.

Main Methods:

  • Co-immunoprecipitation assays to confirm protein-protein interactions.
  • Reporter gene assays to assess transcriptional activation.
  • Mutational analysis to evaluate the importance of CARM1's enzymatic activity.

Main Results:

  • CARM1 directly binds to beta-catenin.
  • CARM1 and beta-catenin function synergistically with p300 to activate AR-mediated transcription.
  • The methyltransferase activity of CARM1 is crucial for this synergistic coactivator function.
  • This synergy is not limited to steroid receptors, as CARM1 and beta-catenin also cooperate with LEF-1/TCF-4.

Conclusions:

  • CARM1 and beta-catenin form a functional coactivator complex for AR.
  • CARM1's enzymatic activity is essential for its synergistic coactivation with beta-catenin.
  • The CARM1-beta-catenin complex represents a novel mechanism for regulating gene transcription beyond steroid receptors.

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