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A methylation-mediator complex in hormone signaling

Wei Xu1, Helen Cho, Shilpa Kadam

  • 1Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

Genes & Development
|January 20, 2004
PubMed

Insights

Nuclear hormone receptors recruit coactivators to promote transcription. This study identifies a new complex linking the methylase CARM1 and the SWI/SNF remodeling complex, revealing a novel regulatory mechanism in nuclear hormone signaling.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Gene Regulation

Background:

  • Nuclear hormone receptors (NRs) regulate transcription by recruiting coactivators.
  • Histone methylation enzymes like CARM1 and ATP-remodeling complexes are individually linked to NR-dependent transcription.
  • A functional link between these systems was previously unidentified.

Purpose of the Study:

  • To investigate the functional and mechanistic linkage between CARM1 and ATP-remodeling complexes in nuclear receptor signaling.
  • To identify and characterize novel coactivator complexes involved in NR-dependent transcription.

Main Methods:

  • Purification of endogenous CARM1-interacting proteins.
  • Identification of the nucleosomal methylation activator complex (NUMAC) using biochemical approaches.
  • In vivo studies examining the coassembly of CARM1 and BRG1 on ER-target genes.

Main Results:

  • The nucleosomal methylation activator complex (NUMAC) was identified, containing CARM1 and SWI/SNF components including BRG1.
  • CARM1 within NUMAC specifically methylates nucleosomal histones and enhances its activity.
  • CARM1 reciprocally stimulates the ATPase activity of BRG1, and they coassemble on ER target genes in vivo.

Conclusions:

  • The association of CARM1 with the SWI/SNF ATP-remodeling complex (NUMAC) defines a new regulatory component in nuclear hormone signaling.
  • This complex cooperatively activates estrogen receptor-dependent transcription.
  • This finding establishes a mechanistic link between histone methylation and nucleosome remodeling in gene activation.

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