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 journalArticle

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

Fingerprint

Gene expression
Gene Expression
Genes
Transcriptional Activation
Protein-Arginine N-Methyltransferases
CREB-Binding Protein
Acetyltransferases
Steroid Receptors
coactivator-associated arginine methyltransferase 1
human PRMT2 protein
Lysine
Chromatin
Cell Survival
Chemical activation
Cells
Inflammation
Proteins

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Covic, M., Hassa, P. O., Saccani, S., Buerki, C., Meier, N. I., Lombardi, C., ... Hottiger, M. O. (2005). Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-κB-dependent gene expression. EMBO Journal, 24(1), 85-96. https://doi.org/10.1038/sj.emboj.7600500

Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-κB-dependent gene expression. / Covic, Marcela; Hassa, Paul O.; Saccani, Simona; Buerki, Christine; Meier, Nadja I.; Lombardi, Cornelia; Imhof, Ralph; Bedford, Mark T.; Natoli, Gioacchino; Hottiger, Michael O.

In: EMBO Journal, Vol. 24, No. 1, 12.01.2005, p. 85-96.

Research output: Contribution to journalArticle

Covic, M, Hassa, PO, Saccani, S, Buerki, C, Meier, NI, Lombardi, C, Imhof, R, Bedford, MT, Natoli, G & Hottiger, MO 2005, 'Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-κB-dependent gene expression', EMBO Journal, vol. 24, no. 1, pp. 85-96. https://doi.org/10.1038/sj.emboj.7600500
Covic, Marcela ; Hassa, Paul O. ; Saccani, Simona ; Buerki, Christine ; Meier, Nadja I. ; Lombardi, Cornelia ; Imhof, Ralph ; Bedford, Mark T. ; Natoli, Gioacchino ; Hottiger, Michael O. / Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-κB-dependent gene expression. In: EMBO Journal. 2005 ; Vol. 24, No. 1. pp. 85-96.
@article{f949bfd58d17418cb78be3a263c00de7,
title = "Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-κB-dependent gene expression",
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.",
keywords = "CARM1, ChIP, Methylation, p300, p65/RelA",
author = "Marcela Covic and Hassa, {Paul O.} and Simona Saccani and Christine Buerki and Meier, {Nadja I.} and Cornelia Lombardi and Ralph Imhof and Bedford, {Mark T.} and Gioacchino Natoli and Hottiger, {Michael O.}",
year = "2005",
month = "1",
day = "12",
doi = "10.1038/sj.emboj.7600500",
language = "English",
volume = "24",
pages = "85--96",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-κB-dependent gene expression

AU - Covic, Marcela

AU - Hassa, Paul O.

AU - Saccani, Simona

AU - Buerki, Christine

AU - Meier, Nadja I.

AU - Lombardi, Cornelia

AU - Imhof, Ralph

AU - Bedford, Mark T.

AU - Natoli, Gioacchino

AU - Hottiger, Michael O.

PY - 2005/1/12

Y1 - 2005/1/12

N2 - 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.

AB - 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.

KW - CARM1

KW - ChIP

KW - Methylation

KW - p300

KW - p65/RelA

UR - http://www.scopus.com/inward/record.url?scp=19944431570&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=19944431570&partnerID=8YFLogxK

U2 - 10.1038/sj.emboj.7600500

DO - 10.1038/sj.emboj.7600500

M3 - Article

C2 - 15616592

AN - SCOPUS:19944431570

VL - 24

SP - 85

EP - 96

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 1

ER -