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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 RIS Download

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 | Serine-Arginine Splicing Factors | Transcription Factors

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Associated grants

  • Agency: NIGMS NIH HHS, Id: R01 GM056244
  • Agency: NIAMS NIH HHS, Id: AR045113
  • Agency: NIGMS NIH HHS, Id: GM56244
  • Agency: NCI NIH HHS, Id: T32 CA009657
  • Agency: NCI NIH HHS, Id: T32 CA09657
  • Agency: NIAMS NIH HHS, Id: R01 AR045113

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