title: Contrasting roles for MyoD in organizing myogenic promoter structures during embryonic skeletal muscle development.
abstract: BACKGROUND
  Among the complexities of skeletal muscle differentiation is a temporal distinction in the onset of expression of different lineage-specific genes. The lineage-determining factor MyoD is bound to myogenic genes at the onset of differentiation whether gene activation is immediate or delayed. How temporal regulation of differentiation-specific genes is established remains unclear.
  
  
  RESULTS
  Using embryonic tissue, we addressed the molecular differences in the organization of the myogenin and muscle creatine kinase (MCK) gene promoters by examining regulatory factor binding as a function of both time and spatial organization during somitogenesis. At the myogenin promoter, binding of the homeodomain factor Pbx1 coincided with H3 hyperacetylation and was followed by binding of co-activators that modulate chromatin structure. MyoD and myogenin binding occurred subsequently, demonstrating that Pbx1 facilitates chromatin remodeling and modification before myogenic regulatory factor binding. At the same time, the MCK promoter was bound by HDAC2 and MyoD, and activating histone marks were largely absent. The association of HDAC2 and MyoD was confirmed by co-immunoprecipitation, proximity ligation assay (PLA), and sequential ChIP.
  
  
  CONCLUSIONS
  MyoD differentially promotes activated and repressed chromatin structures at myogenic genes early after the onset of skeletal muscle differentiation in the developing mouse embryo.
authors.affiliation: Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: Ok Hyun
authors.initials: OH
authors.lastname: Cho
authors.forename: Chandrashekara
authors.initials: C
authors.lastname: Mallappa
authors.forename: J Manuel
authors.initials: JM
authors.lastname: Hernández-Hernández
authors.forename: Jaime A
authors.initials: JA
authors.lastname: Rivera-Pérez
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Imbalzano
mesh_terms: D000818:Animals; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D056464:Histone Deacetylase 2 / Q000096:biosynthesis / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology*; D017570:MyoD Protein / Q000378:metabolism*; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011401:Promoter Regions, Genetic / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C481797:Pbx1 protein, mouse; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D014157:Transcription Factors; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2
keywords: Pbx; gene expression; gene regulation; histone deacetylase; myogenesis; somite