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MyoD targets chromatin remodeling complexes to the myogenin locus prior to forming a stable DNA-bound complex.

The activation of muscle-specific gene expression requires the coordinated action of muscle regulatory proteins and chromatin-remodeling enzymes. Microarray analysis performed in the presence or absence of a dominant-negative BRG1 ATPase demonstrated that approximately one-third of MyoD-induced genes were highly dependent on SWI/SNF enzymes. To understand the mechanism of activation, we performed chromatin immunoprecipitations analyzing the myogenin promoter. We found that H4 hyperacetylation preceded Brg1 binding in a MyoD-dependent manner but that MyoD binding occurred subsequent to H4 modification and Brg1 interaction. In the absence of functional SWI/SNF enzymes, muscle regulatory proteins did not bind to the myogenin promoter, thereby providing evidence for SWI/SNF-dependent activator binding. We observed that the homeodomain factor Pbx1, which cooperates with MyoD to stimulate myogenin expression, is constitutively bound to the myogenin promoter in a SWI/SNF-independent manner, suggesting a two-step mechanism in which MyoD initially interacts indirectly with the myogenin promoter and attracts chromatin-remodeling enzymes, which then facilitate direct binding by MyoD and other regulatory proteins.

Pubmed ID: 15870273

Authors

  • de la Serna IL
  • Ohkawa Y
  • Berkes CA
  • Bergstrom DA
  • Dacwag CS
  • Tapscott SJ
  • Imbalzano AN

Journal

Molecular and cellular biology

Publication Data

May 4, 2005

Associated Grants

  • Agency: NIAMS NIH HHS, Id: AR045113
  • Agency: NIGMS NIH HHS, Id: GM56244
  • Agency: NIGMS NIH HHS, Id: R01 GM056244
  • Agency: NCI NIH HHS, Id: T32 CA09657

Mesh Terms

  • Acetylation
  • Animals
  • Cell Cycle Proteins
  • Cell Differentiation
  • Cell Line
  • Chromatin
  • Chromatin Assembly and Disassembly
  • Chromatin Immunoprecipitation
  • Cyclin-Dependent Kinase Inhibitor p21
  • DNA
  • DNA Helicases
  • DNA-Binding Proteins
  • Histones
  • Homeodomain Proteins
  • Humans
  • Kinetics
  • MEF2 Transcription Factors
  • Mice
  • Models, Genetic
  • Multiprotein Complexes
  • Muscles
  • MyoD Protein
  • Myogenic Regulatory Factors
  • Myogenin
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • Ribonucleoproteins
  • Transcription Factors