MyoD targets TAF3/TRF3 to activate myogenin transcription.
Skeletal muscle differentiation requires a cascade of transcriptional events to control the spatial and temporal expression of muscle-specific genes. Until recently, muscle-specific transcription was primarily attributed to prototypic enhancer-binding factors, while the role of core promoter recognition complexes in directing myogenesis remained unknown. Here, we report the development of a purified reconstituted system to analyze the properties of a TAF3/TRF3 complex in directing transcription initiation at the Myogenin promoter. Importantly, this new complex is required to replace the canonical TFIID to recapitulate MyoD-dependent activation of Myogenin. In vitro and cell-based assays identify a domain of TAF3 that mediates coactivator functions targeted by MyoD. Our findings also suggest changes to CRSP/Mediator in terminally differentiated myotubes. This switching of the core promoter recognition complex during myogenesis allows a more balanced division of labor between activators and TAF coactivators, thus providing another strategy to accommodate cell-specific regulation during metazoan development.
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Maria Divina E
MD
Deato
Michael T
MT
Marr
Theo
T
Sottero
Carla
C
Inouye
Ping
P
Hu
Robert
R
Tjian
D000818:Animals; D002460:Cell Line; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D046912:Multiprotein Complexes; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D017570:MyoD Protein / Q000378:metabolism*; D018008:Myogenin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000378:metabolism; D035182:TATA Box Binding Protein-Like Proteins / Q000378:metabolism*; D035381:TATA-Binding Protein Associated Factors; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000378:metabolism; D024363:Transcription Initiation Site; D015533:Transcriptional Activation
D018398:Homeodomain Proteins; D046912:Multiprotein Complexes; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C503801:Myog protein, mouse; D018008:Myogenin; D021122:Protein Subunits; D011994:Recombinant Proteins; D035182:TATA Box Binding Protein-Like Proteins; D035381:TATA-Binding Protein Associated Factors; C515947:TRF3 protein, mouse; C532029:Taf3 protein, mouse; D015534:Trans-Activators; D035362:Transcription Factor TFIID