The coactivator-associated arginine methyltransferase is necessary for muscle differentiation - CARM1 coactivates myocyte enhancer factor-2

Chen, S. L., Loffler, K. A., Chen, D. G., Stallcup, M. R. and Muscat, G. E. O. (2002) The coactivator-associated arginine methyltransferase is necessary for muscle differentiation - CARM1 coactivates myocyte enhancer factor-2. Journal of Biological Chemistry, 277 6: 4324-4333. doi:10.1074/jbc.M109835200

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Author Chen, S. L.
Loffler, K. A.
Chen, D. G.
Stallcup, M. R.
Muscat, G. E. O.
Title The coactivator-associated arginine methyltransferase is necessary for muscle differentiation - CARM1 coactivates myocyte enhancer factor-2
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2002-01-01
Year available 2002
Sub-type Article (original research)
DOI 10.1074/jbc.M109835200
Open Access Status File (Publisher version)
Volume 277
Issue 6
Start page 4324
End page 4333
Total pages 10
Place of publication Bethesda, USA
Publisher American Society for Biochemistry and Molecular Biology Inc
Language eng
Subject C1
270100 Biochemistry and Cell Biology
780105 Biological sciences
Abstract Studies with the myogenic basic helix-loop-helix and MADS box factors suggest that efficient transactivation is dependent on the recruitment of the steroid receptor coactivator (SRC) and the cofactors p300 and p300/CBP-associated factor. SRCs have been demonstrated to recruit CARM1 (coactivator-associated arginine methyltransferase-1), a member of the S-adenOSyl-L-methionine-dependent PRMTI-5 (protein-arginine N-methyltransferase-1-5) family, which catalyzes the methylation of arginine residues. This prompted us to investigate the functional role of CARM1/PRMT4 during skeletal myogenesis. We demonstrate that CARM1 and the SRC cofactor GRIP-1 cooperatively stimulate the activity of myocyte enhancer factor-2C (MEF2C). Moreover, there are direct interactions among MEF2C, GRIP-1, and CARM1. Chromatin immunoprecipitation demonstrated the in vivo recruitment of MEF2 and CARM1 to the endogenous muscle creatine kinase promoter in a differentiation-dependent manner. Furthermore, CARM1 is expressed in somites during embryogenesis and in the nuclei of muscle cells. Treatment of myogenic cells with the methylation inhibitor adenosine dialdehyde or tet-regulated CARM1 antisense expression did not affect expression of MyoD. However, inhibition of CARM1. inhibited differentiation and abrogated the expression of the key transcription factors (myogenin and MEF2) that initiate the differentiation cascade. This work clearly demonstrates that the arginine methyltransferase CARM1 potentiates myogenesis and supports the positive role of arginine methylation in mammalian differentiation.
Keyword Biochemistry & Molecular Biology
N-methyltransferase
Gene-expression
Binding-factor
Bhlh Proteins
Receptor
Mef2
Activation
Myod
P300
Transcription
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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Created: Wed, 15 Aug 2007, 04:05:11 EST