The myogenic basic helix-loop-helix family of transcription factors shows similar requirements for SWI/SNF chromatin remodeling enzymes during muscle differentiation in culture
Roy, Kanaklata ; de la Serna, Ivana L. ; Imbalzano, Anthony N.
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Faculty Advisor
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UMass Chan Affiliations
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Keywords
Animals
Cell Cycle
Cell Differentiation
Chromatin
Chromosomal Proteins, Non-Histone
Cyclins
*DNA-Binding Proteins
Gene Expression Regulation, Developmental
Helix-Loop-Helix Motifs
Humans
Mice
Muscle Proteins
Muscle, Skeletal
MyoD Protein
Myogenic Regulatory Factor 5
Myogenic Regulatory Factors
Myogenin
*Trans-Activators
Transcription Factors
Cell Biology
Life Sciences
Medicine and Health Sciences
Subject Area
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Abstract
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.
Source
J Biol Chem. 2002 Sep 13;277(37):33818-24. Epub 2002 Jul 8. Link to article on publisher's site