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Regulation of transcription by a protein methyltransferase

D Chen1, H Ma, H Hong

  • 1Department of Pathology HMR 301, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA.

Science (New York, N.Y.)
|June 26, 1999
PubMed

Insights

Coactivator-associated arginine methyltransferase 1 (CARM1) acts as a secondary coactivator by binding to p160 proteins, enhancing nuclear receptor activity. CARM1

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Gene Regulation

Background:

  • The p160 family of coactivators (SRC-1, GRIP1/TIF2, p/CIP) are crucial for transcriptional activation by nuclear hormone receptors.
  • Nuclear receptor-mediated transcription is a key process in various cellular functions and diseases.

Purpose of the Study:

  • To investigate the role of Coactivator-associated arginine methyltransferase 1 (CARM1) in nuclear hormone receptor-mediated transcription.
  • To determine the mechanism by which CARM1 functions as a coactivator.

Main Methods:

  • Co-expression assays to assess CARM1's effect on nuclear receptor transcriptional activity.
  • Biochemical assays to determine CARM1's binding interactions with p160 coactivators.
  • In vitro methylation assays using histone H3.
  • Site-directed mutagenesis to probe the function of the S-adenosylmethionine binding domain of CARM1.

Main Results:

  • CARM1 enhances nuclear receptor transcriptional activation when coexpressed with GRIP1 or SRC-1a, but not alone.
  • CARM1 binds to the carboxyl-terminal region of p160 coactivators, functioning as a secondary coactivator.
  • CARM1 exhibits methyltransferase activity towards histone H3 in vitro.
  • A mutation in CARM1's putative S-adenosylmethionine binding domain significantly impairs both its methyltransferase and coactivator activities.

Conclusions:

  • CARM1 functions as a secondary coactivator by associating with p160 coactivators, thereby enhancing nuclear receptor-mediated transcription.
  • The methyltransferase activity of CARM1, potentially through histone methylation, is linked to its coactivator function.
  • Coactivator-mediated protein methylation represents a novel mechanism contributing to transcriptional regulation.

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