Snail regulates MyoD binding-site occupancy to direct enhancer switching and differentiation-specific transcription in myogenesis

Mol Cell. 2012 Aug 10;47(3):457-68. doi: 10.1016/j.molcel.2012.05.046. Epub 2012 Jul 5.


In skeletal myogenesis, the transcription factor MyoD activates distinct transcriptional programs in progenitors compared to terminally differentiated cells. Using ChIP-Seq and gene expression analyses, we show that in primary myoblasts, Snail-HDAC1/2 repressive complex binds and excludes MyoD from its targets. Notably, Snail binds E box motifs that are G/C rich in their central dinucleotides, and such sites are almost exclusively associated with genes expressed during differentiation. By contrast, Snail does not bind the A/T-rich E boxes associated with MyoD targets in myoblasts. Thus, Snai1-HDAC1/2 prevent MyoD occupancy on differentiation-specific regulatory elements, and the change from Snail to MyoD binding often results in enhancer switching during differentiation. Furthermore, we show that a regulatory network involving myogenic regulatory factors (MRFs), Snai1/2, miR-30a, and miR-206 acts as a molecular switch that controls entry into myogenic differentiation. Together, these results reveal a regulatory paradigm that directs distinct gene expression programs in progenitors versus terminally differentiated cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation / genetics
  • Enhancer Elements, Genetic / physiology*
  • Mice
  • Molecular Sequence Data
  • Muscle Development / genetics*
  • MyoD Protein / chemistry
  • MyoD Protein / genetics
  • MyoD Protein / metabolism*
  • Myoblasts, Skeletal / cytology
  • Myoblasts, Skeletal / physiology*
  • Primary Cell Culture
  • Protein Binding / genetics
  • Snail Family Transcription Factors
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic / physiology


  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Snai1 protein, mouse
  • Snail Family Transcription Factors
  • Transcription Factors

Associated data

  • GEO/GSE24811
  • GEO/GSE24852
  • GEO/GSE24904
  • GEO/GSE38236