MyoD Targets Chromatin Remodeling Complexes to the Myogenin Locus Prior to Forming a Stable DNA-Bound Complex Article (Web of Science)

abstract

  • ABSTRACT 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.

authors

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

publication date

  • 2005

published in

number of pages

  • 12

start page

  • 3997

end page

  • 4009

volume

  • 25

issue

  • 10