Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-κB-dependent gene expression

Marcela Covic, Paul O. Hassa, Simona Saccani, Christine Buerki, Nadja I. Meier, Cornelia Lombardi, Ralph Imhof, Mark T. Bedford, Gioacchino Natoli, Michael O. Hottiger

Research output: Contribution to journalArticlepeer-review

Abstract

Nuclear factor kappaB (NF-κB) 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-κB and functions as a promoter-specific regulator of NF-κB recruitment to chromatin. Carm1 knockout cells showed impaired expression of a subset of NF-κB-dependent genes upon TNFα or LPS stimulation. CARM1 forms a complex with p300 and NF-κB in vivo and interacts directly with the NF-κB subunit p65 in vitro. CARM1 seems to act in a gene-specific manner mainly by enhancing NF-κB recruitment to cognate sites. Moreover, CARM1 synergistically coactivates NF-κB-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-κB 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-κB-dependent gene activation in vivo.

Original languageEnglish
Pages (from-to)85-96
Number of pages12
JournalEMBO Journal
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 12 2005

Keywords

  • CARM1
  • ChIP
  • Methylation
  • p300
  • p65/RelA

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-κB-dependent gene expression'. Together they form a unique fingerprint.

Cite this