Article
- The EMBO Journal (2006) 25, 490 - 501
- doi:10.1038/sj.emboj.7600943
Published online: 19 January 2006
Subject Categories:
Skeletal muscle specification by myogenin and Mef2D via the SWI/SNF ATPase Brg1
Yasuyuki Ohkawa, Concetta GA Marfella and Anthony N Imbalzano
- Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA, USA
Correspondence to:
Anthony N Imbalzano, Department of Cell Biology, University of Massachusetts, Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA. Tel.: +1 508 856 1029; Fax: +1 508 856 5612; E-mail: animbalzano@yahoo.com or anthony.imbalzano@umassmed.edu
Received 5 September 2005; Accepted 14 December 2005
Abstract
Myogenin is required not for the initiation of myogenesis but instead for skeletal muscle formation through poorly understood mechanisms. We demonstrate in cultured cells and, for the first time, in embryonic tissue, that myogenic late genes that specify the skeletal muscle phenotype are bound by MyoD prior to the initiation of gene expression. At the onset of muscle specification, a transition from MyoD to myogenin occurred at late gene loci, concomitant with loss of HDAC2, the appearance of both the Mef2D regulator and the Brg1 chromatin-remodeling enzyme, and the opening of chromatin structure. We further demonstrated that ectopic expression of myogenin and Mef2D, in the absence of MyoD, was sufficient to induce muscle differentiation in a manner entirely dependent on Brg1. These results indicate that myogenin specifies the muscle phenotype by cooperating with Mef2D to recruit an ATP-dependent chromatin-remodeling enzyme that alters chromatin structure at regulatory sequences to promote terminal differentiation.
Keywords:
- Brg1,
- chromatin remodeling,
- Mef2D,
- myogenesis,
- myogenin
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