title: Six1 regulates MyoD expression in adult muscle progenitor cells.
abstract: Quiescent satellite cells are myogenic progenitors that enable regeneration of skeletal muscle. One of the early events of satellite cell activation following myotrauma is the induction of the myogenic regulatory factor MyoD, which eventually induces terminal differentiation and muscle function gene expression. The purpose of this study was to elucidate the mechanism by which MyoD is induced during activation of satellite cells in mouse muscle undergoing regeneration. We show that Six1, a transcription factor essential for embryonic myogenesis, also regulates MyoD expression in muscle progenitor cells. Six1 knock-down by RNA interference leads to decreased expression of MyoD in myoblasts. Chromatin immunoprecipitation assays reveal that Six1 binds the Core Enhancer Region of MyoD. Further, transcriptional reporter assays demonstrate that Core Enhancer Region reporter gene activity in myoblasts and in regenerating muscle depends on the expression of Six1 and on Six1 binding sites. Finally, we provide evidence indicating that Six1 is required for the proper chromatin structure at the Core Enhancer Region, as well as for MyoD binding at its own enhancer. Together, our results reveal that MyoD expression in satellite cells depends on Six1, supporting the idea that Six1 plays an important role in adult myogenesis, in addition to its role in embryonic muscle formation.
authors.affiliation: Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Yubing
authors.initials: Y
authors.lastname: Liu
authors.forename: Imane
authors.initials: I
authors.lastname: Chakroun
authors.forename: Dabo
authors.initials: D
authors.lastname: Yang
authors.forename: Ellias
authors.initials: E
authors.lastname: Horner
authors.forename: Jieyi
authors.initials: J
authors.lastname: Liang
authors.forename: Arif
authors.initials: A
authors.lastname: Aziz
authors.forename: Alphonse
authors.initials: A
authors.lastname: Chu
authors.forename: Yves
authors.initials: Y
authors.lastname: De Repentigny
authors.forename: F Jeffrey
authors.initials: FJ
authors.lastname: Dilworth
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kothary
authors.forename: Alexandre
authors.initials: A
authors.lastname: Blais
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002843:Chromatin / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism / Q000502:physiology; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics / Q000502:physiology; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D018398:Homeodomain Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018006:Myogenic Regulatory Factors; C490947:Six1 protein, mouse; D014157:Transcription Factors