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

نویسندگان

  • Ivana L de la Serna
  • Yasuyuki Ohkawa
  • Charlotte A Berkes
  • Donald A Bergstrom
  • Caroline S Dacwag
  • Stephen J Tapscott
  • Anthony N Imbalzano
چکیده

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.

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عنوان ژورنال:
  • Molecular and cellular biology

دوره 25 10  شماره 

صفحات  -

تاریخ انتشار 2005