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J. Biol. Chem., Vol. 282, Issue 52, 37650-37659, December 28, 2007

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MyoD Acetylation Influences Temporal Patterns of Skeletal Muscle Gene Expression^*

Monica Di Padova¹², Giuseppina Caretti¹, Po Zhao, Eric P. Hoffman, and Vittorio Sartorelli³

From the Laboratory of Muscle Stem Cells and Gene Regulation, NIAMS, National Institutes of Health, Bethesda, Maryland 20829 and the Research Center for Genetic Medicine and Children's National Medical Center, Washington, D. C. 20010

MyoD is sufficient to initiate the skeletal muscle gene expression program. Transcription of certain MyoD target genes occurs in the early phases, whereas that of others is induced only at later stages, although MyoD is present throughout the differentiation process. MyoD acetylation regulates transcriptional competency, yet whether this post-translational modification is equally relevant for activation of all the MyoD targets is unknown. Moreover, the molecular mechanisms through which acetylation ensures that MyoD achieves its optimal activity remain unexplored. To address these two outstanding issues, we have coupled genome-wide expression profiling and chromatin immunoprecipitation in a model system in which MyoD or its nonacetylatable version was inducibly activated in mouse embryonic fibroblasts derived from MyoD^-/-/Myf5^-/- mice. Our results reveal that MyoD acetylation influences transcription of selected genes expressed at defined stages of the muscle program by regulating chromatin access of MyoD, histone acetylation, and RNA polymerase II recruitment.

Received for publication, August 30, 2007 , and in revised form, October 24, 2007.

^* This work was supported in part by the Intramural Research Program of NIAMS, National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Tables S1–S6.

¹ Both authors contributed equally to this work.

² Present address: Dept. of Experimental Medicine, University of L'Aquila, L'Aquila 67100, Italy.

³ To whom correspondence should be addressed: Laboratory of Muscle Stem Cells and Gene Regulation, 50 South Dr., Rm. 1351, NIAMS, National Institutes of Health, Bethesda, MD 20892. Tel.: 301-435-8145; Fax: 301-480-9699; E-mail: sartorev{at}mail.nih.gov.

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