A methylation-mediator complex in hormone signaling

Wei Xu, Helen Cho, Shilpa Kadam, Ester M. Banayo, Scott Anderson, John R. Yates, Beverly M. Emerson, Ronald M. Evans

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

The recruitment of coactivators by nuclear hormone receptors (NRs) promotes transcription by subverting chromatin-mediated repression. Although the histone methylation enzyme CARM1 and an ATP-remodeling complex have been individually implicated in nuclear receptor-dependent transcription, neither a functional nor mechanistic linkage between these systems has been identified. In the process of purifying endogenous CARM1-interacting proteins, we identified an associated complex, nucleosomal methylation activator complex (NUMAC), which includes at least eight components of SWI/SNF, including the ATPase BRG1. In the NUMAC complex, the methylase, CARM1, acquires the ability to covalently modify nucleosomal histones, and the directed nucleosome versus free core histone methylation-specificity change is increased dramatically. Reciprocally, CARM1 stimulates the ATPase activity of BRG1, a key component in nucleosome remodeling. In vivo, CARM1 and BRG1 coassemble on an estrogen receptor (ER)-target gene to cooperatively activate ER-dependent transcription. This association of ATP-remodeling factors with HMT CARM1 defines a new component of regulation in the nuclear hormone-signaling pathway.

Original languageEnglish (US)
Pages (from-to)144-156
Number of pages13
JournalGenes and Development
Volume18
Issue number2
DOIs
StatePublished - Jan 15 2004

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Keywords

  • CARM1
  • Chromatin remodeling
  • Histone methyltransferase
  • SWI/SNF

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Xu, W., Cho, H., Kadam, S., Banayo, E. M., Anderson, S., Yates, J. R., Emerson, B. M., & Evans, R. M. (2004). A methylation-mediator complex in hormone signaling. Genes and Development, 18(2), 144-156. https://doi.org/10.1101/gad.1141704