title: Epigenetic regulation of skeletal muscle development and differentiation.
abstract: Skeletal muscle cells have served as a paradigm for understanding mechanisms leading to cellular differentiation. Formation of skeletal muscle involves a series of steps in which cells are committed towards the myogenic lineage, undergo expansion to give rise to myoblasts that differentiate into multinucleated myotubes, and mature to form adult muscle fibers. The commitment, proliferation, and differentiation of progenitor cells involve both genetic and epigenetic changes that culminate in alterations in gene expression. Members of the Myogenic regulatory factor (MRF), as well as the Myocyte Enhancer Factor (MEF2) families control distinct steps of skeletal muscle proliferation and differentiation. In addition, -growing evidence indicates that chromatin modifying enzymes and remodeling complexes epigenetically reprogram muscle promoters at various stages that preclude or promote MRF and MEF2 activites. Among these, histone deacetylases (HDACs), histone acetyltransferases (HATs), histone methyltransferases (HMTs) and SWI/SNF complexes alter chromatin structure through post-translational modifications to impact MRF and MEF2 activities. With such new and emerging knowledge, we are beginning to develop a true molecular understanding of the mechanisms by which skeletal muscle development and differentiation is regulated. Elucidation of the mechanisms by which epigenetic regulators control myogenesis will likely provide a new foundation for the development of novel therapeutic drugs for muscle dystrophies, ageing-related regeneration defects that occur due to altered proliferation and differentiation, and other malignancies.
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD9, 2 Medical Drive, Singapore, 117597, Singapore.
authors.forename: Narendra
authors.initials: N
authors.lastname: Bharathy
authors.forename: Belinda Mei Tze
authors.initials: BM
authors.lastname: Ling
authors.forename: Reshma
authors.initials: R
authors.lastname: Taneja
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D042002:Chromatin Assembly and Disassembly; D044127:Epigenesis, Genetic / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D024510:Muscle Development / Q000187:drug effects / Q000235:genetics*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D009136:Muscular Dystrophies / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D056572:Histone Deacetylase Inhibitors; D014157:Transcription Factors