Pbx marks genes for activation by MyoD indicating a role for a homeodomain protein in establishing myogenic potential.
Skeletal muscle differentiation is initiated by the transcription factor MyoD, which binds directly to the regulatory regions of genes expressed during skeletal muscle differentiation and initiates chromatin remodeling at specific promoters. It is not known, however, how MyoD initially recognizes its binding site in a chromatin context. Here we show that the H/C and helix III domains, two domains of MyoD that are necessary for the initiation of chromatin remodeling at the myogenin locus, together regulate a restricted subset of genes, including myogenin. These domains are necessary for the stable binding of MyoD to the myogenin promoter through an interaction with an adjacent protein complex containing the homeodomain protein Pbx, which appears to be constitutively bound at this site. This demonstrates a specific mechanism of targeting MyoD to loci in inactive chromatin and reveals a critical role of homeodomain proteins in marking specific genes for activation in the muscle lineage.
Berkes
Charlotte A
CA
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Bergstrom
Donald A
DA
Penn
Bennett H
BH
Seaver
Karen J
KJ
Knoepfler
Paul S
PS
Tapscott
Stephen J
SJ
D000818:Animals; D001483:Base Sequence / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011401:Promoter Regions, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics*
D005819:Genetic Markers; D018398:Homeodomain Proteins; D046911:Macromolecular Substances; D017570:MyoD Protein; C481797:Pbx1 protein, mouse; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D014157:Transcription Factors