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CARM1 but not its enzymatic activity is required for transcriptional coactivation of NF-kappaB-dependent gene expression


Jayne, S; Rothgiesser, K M; Hottiger, M O (2009). CARM1 but not its enzymatic activity is required for transcriptional coactivation of NF-kappaB-dependent gene expression. Journal of Molecular Biology, 394(3):485-495.

Abstract

Coactivator-associated arginine methyltransferase 1 (CARM1) belongs to the protein arginine methyltransferase family. It was reported to methylate histone as well as non-histone proteins and thus to be involved in transcriptional activation and mRNA degradation/stability. Here we report the genetic complementation of carm1-/- cells with wild-type CARM1 or an enzymatic inactive mutant of CARM1 to investigate the requirement of CARM1 and its enzymatic activity for nuclear factor kappaB (NF-kappaB)-dependent gene expression. Using custom microarray and quantitative reverse transcription PCR, we could define a subset of NF-kappaB target genes that required CARM1 for their proper expression. Although several tumor necrosis factor-alpha- and phorbol-12-myristate-13-acetate/ionomycin-induced NF-kappaB target genes are CARM1 dependent, CARM1 enzymatic activity was dispensable for gene expression. Interestingly, CARM1 was not required for the stimulus-dependent recruitment of RelA/p65 to chromatin, suggesting that CARM1 is rather contributing in protein complex stabilization. Together, our results confirm the importance of CARM1 as transcriptional cofactor without the involvement of its catalytic activity.

Abstract

Coactivator-associated arginine methyltransferase 1 (CARM1) belongs to the protein arginine methyltransferase family. It was reported to methylate histone as well as non-histone proteins and thus to be involved in transcriptional activation and mRNA degradation/stability. Here we report the genetic complementation of carm1-/- cells with wild-type CARM1 or an enzymatic inactive mutant of CARM1 to investigate the requirement of CARM1 and its enzymatic activity for nuclear factor kappaB (NF-kappaB)-dependent gene expression. Using custom microarray and quantitative reverse transcription PCR, we could define a subset of NF-kappaB target genes that required CARM1 for their proper expression. Although several tumor necrosis factor-alpha- and phorbol-12-myristate-13-acetate/ionomycin-induced NF-kappaB target genes are CARM1 dependent, CARM1 enzymatic activity was dispensable for gene expression. Interestingly, CARM1 was not required for the stimulus-dependent recruitment of RelA/p65 to chromatin, suggesting that CARM1 is rather contributing in protein complex stabilization. Together, our results confirm the importance of CARM1 as transcriptional cofactor without the involvement of its catalytic activity.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Biochemistry and Molecular Biology
Dewey Decimal Classification:570 Life sciences; biology
Date:2009
Deposited On:01 Mar 2010 14:43
Last Modified:05 Apr 2016 14:01
Publisher:Elsevier
ISSN:0022-2836
Publisher DOI:https://doi.org/10.1016/j.jmb.2009.09.032
PubMed ID:19769987

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