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Molecular and Cellular Biology, January 2007, p. 384-394, Vol. 27, No. 1
0270-7306/07/$08.00+0     doi:10.1128/MCB.01528-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Protein Arginine Methyltransferase Prmt5 Is Required for Myogenesis because It Facilitates ATP-Dependent Chromatin Remodeling{triangledown}

Caroline S. Dacwag,1 Yasuyuki Ohkawa,1 Sharmistha Pal,2 Saïd Sif,2 and Anthony N. Imbalzano1*

Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655,1 Department of Molecular and Cellular Biochemistry, The Ohio State University College of Medicine, 1645 Neil Avenue, Columbus, Ohio 432102

Received 16 August 2006/ Returned for modification 25 September 2006/ Accepted 4 October 2006

Skeletal muscle differentiation requires the coordinated activity of transcription factors, histone modifying enzymes, and ATP-dependent chromatin remodeling enzymes. The type II protein arginine methyltransferase Prmt5 symmetrically dimethylates histones H3 and H4 and numerous nonchromatin proteins, and prior work has implicated Prmt5 in transcriptional repression. Here we demonstrate that MyoD-induced muscle differentiation requires Prmt5. One of the first genes activated during differentiation encodes the myogenic regulator myogenin. Prmt5 and dimethylated H3R8 (histone 3 arginine 8) are localized at the myogenin promoter in differentiating cells. Modification of H3R8 required Prmt5, and reduction of Prmt5 resulted in the abrogation of promoter binding by the Brg1 ATPase-associated with the SWI/SNF chromatin remodeling enzymes and all subsequent events associated with gene activation, including increases in chromatin accessibility and stable binding by MyoD. Prmt5 and dimethylated H3R8 were also associated with the myogenin promoter in activated satellite cells isolated from muscle tissue, further demonstrating the physiological relevance of these observations. The data indicate that Prmt5 facilitates myogenesis because it is required for Brg1-dependent chromatin remodeling and gene activation at a locus essential for differentiation. We therefore conclude that a histone modifying enzyme is necessary to permit an ATP-dependent chromatin remodeling enzyme to function.

* Corresponding author. Mailing address: Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655. Phone: (508) 856-1029. Fax: (508) 856-5612. E-mail: anthony.imbalzano{at}umassmed.edu.

{triangledown} Published ahead of print on 16 October 2006.

Molecular and Cellular Biology, January 2007, p. 384-394, Vol. 27, No. 1
0270-7306/07/$08.00+0     doi:10.1128/MCB.01528-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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