Article
- The EMBO Journal (2005) 24, 85 - 96
- doi:10.1038/sj.emboj.7600500
Published online: 16 December 2004
Subject Category:
Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-
B-dependent gene expression
Marcela Covic1,a, Paul O Hassa1,a, Simona Saccani2, Christine Buerki1, Nadja I Meier1, Cornelia Lombardi1, Ralph Imhof1, Mark T Bedford3, Gioacchino Natoli2 and Michael O Hottiger1
- Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich, Switzerland
- Institute for Research in Biomedicine, Bellinzona, Switzerland
- Department of Carcinogenesis, University of Texas, Smithville, TX, USA
Correspondence to:
Michael O Hottiger, Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. Tel.: +41 1 635 5474; Fax: +41 1 635 6840; E-mail: hottiger@vetbio.unizh.ch
aThese two authors contributed equally to this work
Received 9 July 2004; Accepted 9 November 2004
Abstract
Nuclear factor kappaB (NF-
B) plays an important role in the transcriptional regulation of genes involved in inflammation and cell survival. Here, we show that coactivator-associated arginine methyltransferase CARM1/PRMT4 is a novel transcriptional coactivator of NF-B and functions as a promoter-specific regulator of NF-B recruitment to chromatin. Carm1 knockout cells showed impaired expression of a subset of NF-B-dependent genes upon TNF
or LPS stimulation. CARM1 forms a complex with p300 and NF-B in vivo and interacts directly with the NF-B subunit p65 in vitro. CARM1 seems to act in a gene-specific manner mainly by enhancing NF-B recruitment to cognate sites. Moreover, CARM1 synergistically coactivates NF-B-mediated transactivation, in concert with the transcriptional coactivators p300/CREB-binding protein and the p160 family of steroid receptor coactivators. For at least a subset of CARM1-dependent NF-B target genes, the enzymatic activities of both CARM1 and p300 are necessary for the observed synergy between CARM1 and p300. Our results suggest that the cooperative action between protein arginine methyltransferases and protein lysine acetyltransferases regulates NF-B-dependent gene activation in vivo.
Keywords:
- CARM1,
- ChIP,
- p300,
- p65/RelA,
- methylation
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