Article ; Online: Regulating a master regulator: establishing tissue-specific gene expression in skeletal muscle.
Epigenetics
2010 Volume 5, Issue 8, Page(s) 691–695
Abstract: MyoD is a master regulator of the skeletal muscle gene expression program. ChIP-Seq analysis has ... gene expression program. Thus Mef2d, Six4, and p38α MAPK function coordinately as regulators of a master regulator ... on studies of the muscle-specific myog gene, we propose a model where the transcriptional activators Mef2d ...
| Abstract | MyoD is a master regulator of the skeletal muscle gene expression program. ChIP-Seq analysis has recently revealed that MyoD binds to a large number of genomic loci in differentiating myoblasts, yet only activates transcription at a subset of these genes. Here we discuss recent data suggesting that the ability of MyoD to mediate gene expression is regulated through the function of Polycomb and Trithorax Group proteins. Based on studies of the muscle-specific myog gene, we propose a model where the transcriptional activators Mef2d and Six4 mediate recruitment of Trithorax Group proteins Ash2L/MLL2 and UTX to MyoD-bound promoters to overcome the Polycomb-mediated repression of muscle genes. Modulation of the interaction between Ash2L/MLL2 and Mef2d by the p38α MAPK signaling pathway in turns provides fine-tuning of the muscle-specific gene expression program. Thus Mef2d, Six4, and p38α MAPK function coordinately as regulators of a master regulator to mediate expression of MyoD target genes. |
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| MeSH term(s) | Animals ; Cell Differentiation/physiology ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Gene Expression Regulation/physiology ; Genetic Loci/physiology ; Histone Demethylases ; Histone-Lysine N-Methyltransferase ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Humans ; MADS Domain Proteins/genetics ; MADS Domain Proteins/metabolism ; MAP Kinase Signaling System/physiology ; MEF2 Transcription Factors ; Models, Biological ; Muscle, Skeletal/metabolism ; Myeloid-Lymphoid Leukemia Protein/genetics ; Myeloid-Lymphoid Leukemia Protein/metabolism ; MyoD Protein/biosynthesis ; MyoD Protein/genetics ; Myoblasts/metabolism ; Myogenic Regulatory Factors/genetics ; Myogenic Regulatory Factors/metabolism ; Myogenin/genetics ; Myogenin/metabolism ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Organ Specificity/physiology ; Polycomb-Group Proteins ; Promoter Regions, Genetic/physiology ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Trans-Activators/genetics ; Trans-Activators/metabolism ; p38 Mitogen-Activated Protein Kinases/genetics ; p38 Mitogen-Activated Protein Kinases/metabolism |
| Chemical Substances | DNA-Binding Proteins ; Homeodomain Proteins ; KMT2A protein, human ; KMT2D protein, human ; MADS Domain Proteins ; MEF2 Transcription Factors ; MEF2D protein, human ; MYOG protein, human ; MyoD Protein ; MyoD1 myogenic differentiation protein ; Myogenic Regulatory Factors ; Myogenin ; Neoplasm Proteins ; Nuclear Proteins ; Polycomb-Group Proteins ; Repressor Proteins ; SIX4 protein, human ; Trans-Activators ; Myeloid-Lymphoid Leukemia Protein (149025-06-9) ; Histone Demethylases (EC 1.14.11.-) ; KDM6A protein, human (EC 1.14.11.-) ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24) |
| Language | English |
| Publishing date | 2010-11-01 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Review |
| ISSN | 1559-2308 |
| ISSN (online) | 1559-2308 |
| DOI | 10.4161/epi.5.8.13045 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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