Myocyte Enhancer Factor 2 Acetylation by p300 Enhances Its DNA Binding Activity, Transcriptional Activity, and Myogenic Differentiation

Abstract

Myocyte enhancer factor 2 (MEF2) family proteins are key transcription factors controlling gene expression in myocytes, lymphocytes, and neurons. MEF2 proteins are known to be regulated by phosphorylation. We now provide evidence showing that MEF2C is acetylated by p300 both in vitro and in vivo. In C2C12 myogenic cells, MEF2 is preferentially acetylated in differentiating myocytes but not in undifferentiated myoblasts. Several major acetylation sites are mapped to the transactivation domain of MEF2C, some of which are fully conserved in other MEF2 members from several different species. Mutation of these lysines affects MEF2 DNA binding and transcriptional activity, as well as its synergistic effect with myogenin in myogenic conversion assays. When introduced into C2C12 myoblasts, the nonacetylatable MEF2C inhibits myogenic differentiation. Thus, in addition to phosphorylation, MEF2 activity is also critically regulated by acetylation during myogenesis.

ACKNOWLEDGMENTS

We thank P. L. Puri (Burnham Institute, Calif.) and X. J. Yang (McGill University) for reagents, R. Derynck (UCSF) for helpful suggestions, L. Yu in our group for initial findings, and L. Sun and C. Wong for technical assistance.

This work was supported by grants from the Hong Kong Research Grant Council (HKUST6139/03M to G.Z. and HKUST6143/03 M to Z.W.), EHIA funding for cell signaling studies from HKUST, and the Areas of Excellence scheme established under the University Grants Committee of the Hong Kong Special Administrative Region, China (project AoE/B-15/01).