title: A methylation-mediator complex in hormone signaling.
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.
authors.affiliation: Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Helen
authors.initials: H
authors.lastname: Cho
authors.forename: Shilpa
authors.initials: S
authors.lastname: Kadam
authors.forename: Ester M
authors.initials: EM
authors.lastname: Banayo
authors.forename: Scott
authors.initials: S
authors.lastname: Anderson
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Beverly M
authors.initials: BM
authors.lastname: Emerson
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Evans
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000302:isolation & purification / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D046911:Macromolecular Substances; D018160:Receptors, Cytoplasmic and Nuclear; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D008780:Methyltransferases; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1