Genes up-regulated in NIH 3T3 cells (fibroblasts) 24 h after inducing MYOD [GeneID=4654] which were down-regulated by dominant negative form of SMARCA4 [GeneID=6597].
Full description or 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.
Collection
C2: Curated CGP: Chemical and Genetic Perturbations
Source publication
Pubmed 15870273 Authors: de la Serna IL,Ohkawa Y,Berkes CA,Bergstrom DA,Dacwag CS,Tapscott SJ,Imbalzano AN
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