A methylation-mediator complex in hormone signaling.
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.
Xu
Wei
W
Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Cho
Helen
H
Kadam
Shilpa
S
Banayo
Ester M
EM
Anderson
Scott
S
Yates
John R
JR
Emerson
Beverly M
BM
Evans
Ronald M
RM
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*
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