A methylation-mediator complex in hormone signaling
- Wei Xu1,
- Helen Cho1,
- Shilpa Kadam2,
- Ester M. Banayo1,
- Scott Anderson3,
- John R. Yates III3,
- Beverly M. Emerson2, and
- Ronald M. Evans1,4
- 1Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA; 2Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA; 3Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
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.
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Footnotes
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Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1141704.
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↵4 Corresponding author. E-MAIL evans{at}salk.edu; FAX (858) 455-1349.
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- Accepted December 11, 2003.
- Received August 4, 2003.
- Cold Spring Harbor Laboratory Press