A methylation-mediator complex in hormone signaling

• Published in: Genes & development 2004-01, Vol.18 (2), p.144-156
• Main Authors: Xu, Wei, Cho, Helen, Kadam, Shilpa, Banayo, Ester M, Anderson, Scott, Yates, 3rd, John R, Emerson, Beverly M, Evans, Ronald M
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Animals; CARM1 protein; Chromosomal Proteins, Non-Histone - metabolism; coactivators; Humans; Macromolecular Substances; Methylation; Methyltransferases - metabolism; Protein-Arginine N-Methyltransferases - isolation & purification; Protein-Arginine N-Methyltransferases - metabolism; Receptors, Cytoplasmic and Nuclear - metabolism; Research Papers; Signal Transduction - physiology; Substrate Specificity; SWI/SNF complex; Transcription Factors - metabolism
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.1141704

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.