Genome-wide MyoD Binding in Skeletal Muscle Cells: A Potential for Broad Cellular Reprogramming

Yi Cao, Zizhen Yao, Deepayan Sarkar, Michael Lawrence, Gilson J. Sanchez, Maura H. Parker, Kyle L. MacQuarrie, Jerry Davison, Martin T. Morgan, Walter L. Ruzzo, Robert C. Gentleman*, Stephen J. Tapscott

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

317 Scopus citations

Abstract

Recent studies have demonstrated that MyoD initiates a feed-forward regulation of skeletal muscle gene expression, predicting that MyoD binds directly to many genes expressed during differentiation. We have used chromatin immunoprecipitation and high-throughput sequencing to identify genome-wide binding of MyoD in several skeletal muscle cell types. As anticipated, MyoD preferentially binds to a VCASCTG sequence that resembles the in vitro-selected site for a MyoD:E-protein heterodimer, and MyoD binding increases during differentiation at many of the regulatory regions of genes expressed in skeletal muscle. Unanticipated findings were that MyoD was constitutively bound to thousands of additional sites in both myoblasts and myotubes, and that the genome-wide binding of MyoD was associated with regional histone acetylation. Therefore, in addition to regulating muscle gene expression, MyoD binds genome wide and has the ability to broadly alter the epigenome in myoblasts and myotubes.

Original languageEnglish (US)
Pages (from-to)662-674
Number of pages13
JournalDevelopmental Cell
Volume18
Issue number4
DOIs
StatePublished - Apr 2010

Keywords

  • DNA
  • Devbio
  • Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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