The myogenic basic helix-loop-helix family of transcription factors shows similar requirements for SWI/SNF chromatin remodeling enzymes during muscle differentiation in culture.
The myogenic basic helix-loop-helix family of transcription factors, MyoD, Myf5, myogenin, and MRF4, can each activate the muscle differentiation program when ectopically expressed in non-muscle cells. SWI/SNF complexes are ATP-dependent chromatin remodeling enzymes. We demonstrated previously that SWI/SNF enzymes promote MyoD-mediated muscle differentiation. To ascertain the requirement for SWI/SNF enzymes in muscle differentiation mediated by different MyoD family members, we examined MyoD, Myf5, MRF4, and myogenin-mediated induction of muscle differentiation in cells expressing dominant negative versions of BRG1 or BRM-based SWI/SNF enzymes. We demonstrated that expression of dominant negative BRG1 or BRM inhibited the induction of muscle-specific gene expression by Myf5 and MRF4; however, myogenin failed to induce measurable quantities of muscle-specific mRNAs, even in cells not expressing dominant negative SWI/SNF. In contrast, all four myogenic regulators induced expression of the cell cycle regulators p21, Rb, and cyclin D3 and promoted cell cycle arrest independently of the SWI/SNF enzymes. We proposed that SWI/SNF enzymes are required for the induction of all muscle-specific gene expression by MyoD, Myf5, and MRF4, whereas induction of the cell cycle regulators, p21, Rb, and cyclin D3 occurred independently of SWI/SNF function.
Roy
Kanaklata
K
Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue N., Worcester, MA 01655, USA.
de la Serna
Ivana L
IL
Imbalzano
Anthony N
AN
D016475:3T3 Cells; D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology*; D056743:Cyclin D3; D016213:Cyclins / Q000032:analysis; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051379:Mice; D009124:Muscle Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000196:embryology*; D017570:MyoD Protein / Q000502:physiology*; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors / Q000502:physiology*; D018008:Myogenin / Q000502:physiology; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology*
C534696:CCND3 protein, human; C534697:Ccnd3 protein, mouse; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D056743:Cyclin D3; D016213:Cyclins; D004268:DNA-Binding Proteins; C497417:MYF5 protein, human; C503799:MYOG protein, human; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; C503801:Myog protein, mouse; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D018008:Myogenin; C445179:SWI-SNF-B chromatin-remodeling complex; D015534:Trans-Activators; D014157:Transcription Factors; C063403:myogenic factor 6