Promoter-specific regulation of MyoD binding and signal transduction cooperate to pattern gene expression.
We used expression arrays and chromatin immunoprecipitation assays to demonstrate that myogenesis consists of discrete subprograms of gene expression regulated by MyoD. Approximately 5% of assayed genes alter expression in a specific temporal sequence, and more than 1% are regulated by MyoD without the synthesis of additional transcription factors. MyoD regulates genes expressed at different times during myogenesis, and promoter-specific regulation of MyoD binding is a major mechanism of patterning gene expression. In addition, p38 kinase activity is necessary for the expression of a restricted subset of genes regulated by MyoD, but not for MyoD binding. The identification of distinct molecular mechanisms that regulate discrete subprograms of myogenesis should facilitate analyses of differentiation in normal development and disease.
Bergstrom
Donald A
DA
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Penn
Bennett H
BH
Strand
Andrew
A
Perry
Robert L S
RL
Rudnicki
Michael A
MA
Tapscott
Stephen J
SJ
D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D024510:Muscle Development / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases
D006657:Histones; D017570:MyoD Protein; D011993:Recombinant Fusion Proteins; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases