title: Spatial re-organization of myogenic regulatory sequences temporally controls gene expression.
abstract: During skeletal muscle differentiation, the activation of some tissue-specific genes occurs immediately while others are delayed. The molecular basis controlling temporal gene regulation is poorly understood. We show that the regulatory sequences, but not other regions of genes expressed at late times of myogenesis, are in close physical proximity in differentiating embryonic tissue and in differentiating culture cells, despite these genes being located on different chromosomes. Formation of these inter-chromosomal interactions requires the lineage-determinant MyoD and functional Brg1, the ATPase subunit of SWI/SNF chromatin remodeling enzymes. Ectopic expression of myogenin and a specific Mef2 isoform induced myogenic differentiation without activating endogenous MyoD expression. Under these conditions, the regulatory sequences of late gene loci were not in close proximity, and these genes were prematurely activated. The data indicate that the spatial organization of late genes contributes to temporal regulation of myogenic transcription by restricting late gene expression during the early stages of myogenesis.
authors: Department of Advanced Medical Initiatives, JST-CREST, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
authors: Akihito
authors: A
authors: Harada
authors: Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors: Chandrashekara
authors: C
authors: Mallappa
authors: Department of Advanced Medical Initiatives, JST-CREST, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
authors: Seiji
authors: S
authors: Okada
authors: Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors: John T
authors: JT
authors: Butler
authors: Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors: Stephen P
authors: SP
authors: Baker
authors: Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors: Jeanne B
authors: JB
authors: Lawrence
authors: Department of Advanced Medical Initiatives, JST-CREST, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA anthony.imbalzano@umassmed.edu.
authors: Yasuyuki
authors: Y
authors: Ohkawa
authors: Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA anthony.imbalzano@umassmed.edu.
authors: Anthony N
authors: AN
authors: Imbalzano
mesh_terms: D000818:Animals; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D033481:Chromosomes, Mammalian; D004265:DNA Helicases / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D056464:Histone Deacetylase 2 / Q000502:physiology; D051379:Mice; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism; D017570:MyoD Protein / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology; D011401:Promoter Regions, Genetic; D050436:Regulatory Elements, Transcriptional; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology
chemical_list: D017570:MyoD Protein; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D056464:Histone Deacetylase 2; C513194:Smarca4 protein, mouse; D004265:DNA Helicases
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