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Molecular and Cellular Biology, April 2009, p. 1909-1921, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.00742-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Distinct Protein Arginine Methyltransferases Promote ATP-Dependent Chromatin Remodeling Function at Different Stages of Skeletal Muscle Differentiation{triangledown}

Caroline S. Dacwag,1 Mark T. Bedford,2 Saïd Sif,3 and Anthony N. Imbalzano1*

Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655,1 Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, P.O. Box 389, Smithville, Texas 78957,2 Department of Molecular and Cellular Biochemistry, The Ohio State University College of Medicine, 1645 Neil Ave., Columbus, Ohio 432103

Received 8 May 2008/ Returned for modification 28 May 2008/ Accepted 21 January 2009

Temporal regulation of gene expression is a hallmark of cellular differentiation pathways, yet the mechanisms controlling the timing of expression for different classes of differentiation-specific genes are not well understood. We previously demonstrated that the class II arginine methyltransferase Prmt5 was required for skeletal muscle differentiation at the early stages of myogenesis (C. S. Dacwag, Y. Ohkawa, S. Pal, S. Sif, and A. N. Imbalzano, Mol. Cell. Biol. 27:384-394, 2007). Specifically, when Prmt5 levels were reduced, the ATP-dependent SWI/SNF chromatin-remodeling enzymes could not interact with or remodel the promoter of myogenin, an essential early gene. Here we investigated the requirement for Prmt5 and the class I arginine methyltransferase Carm1/Prmt4 in the temporal control of myogenesis. Both arginine methyltransferases could bind to and modify histones at late-gene regulatory sequences. However, the two enzymes showed sequential requirements for gene expression. Prmt5 was required for early-gene expression but dispensable for late-gene expression. Carm1/Prmt4 was required for late- but not for early-gene expression. The reason for the requirement for Carm1/Prmt4 at late genes was to facilitate SWI/SNF chromatin-remodeling enzyme interaction and remodeling at late-gene loci. Thus, distinct arginine methyltransferases are employed at different times of skeletal muscle differentiation for the purpose of facilitating ATP-dependent chromatin-remodeling enzyme interaction and function at myogenic genes.

* 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 2 February 2009.

Molecular and Cellular Biology, April 2009, p. 1909-1921, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.00742-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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