MyoD acetylation influences temporal patterns of skeletal muscle gene expression.
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.
Di Padova
Monica
M
Laboratory of Muscle Stem Cells and Gene Regulation, NIAMS, National Institutes of Health, Bethesda, MD 20829, USA.
Caretti
Giuseppina
G
Zhao
Po
P
Hoffman
Eric P
EP
Sartorelli
Vittorio
V
D000818:Animals; D019070:Cell Lineage; D002843:Chromatin / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D018482:Muscle, Skeletal / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism* / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D012319:RNA Polymerase II / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
D002843:Chromatin; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D012319:RNA Polymerase II