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

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Molecular and cellular biology, ISSN: 0270-7306, Vol: 25, Issue: 10, Page: 3997-4009

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de la Serna, Ivana L.; Ohkawa, Yasuyuki; Berkes, Charlotte A.; Bergstrom, Donald A.; Dacwag, Caroline S.; Tapscott, Stephen J.; Imbalzano, Anthony N.
American Society for Microbiology
Biochemistry, Genetics and Molecular Biology; 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; Mice; Models, Genetic; Multiprotein Complexes; Muscles; MyoD Protein; Myogenic Regulatory Factors; Myogenin; Nerve Tissue Proteins; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; Promoter Regions (Genetics); Ribonucleoproteins; Transcription Factors; Cell Biology; Life Sciences; Medicine and Health Sciences
article description
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.