NDLI: MyoD is functionally linked to the silencing of a muscle-specific regulatory gene prior to skeletal myogenesis.

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MyoD is functionally linked to the silencing of a muscle-specific regulatory gene prior to skeletal myogenesis.

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MyoD is functionally linked to the silencing of a muscle-specific regulatory gene prior to skeletal myogenesis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Mal, Asoke Harter, Marian L.
Description	Author Affiliation: Mal A ( Department of Molecular Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.);
Abstract	Most of the genes that are central to the process of skeletal muscle differentiation remain in a transcriptionally silent or 'off' state until muscle cells (myoblasts) are induced to differentiate. Although the mechanisms that contribute to this phenomenon are still unclear, it is likely that histone deacetylases (HDACs), which play an important role in the repression of genes, are principally involved. Recent studies indicate that the initiator of the myogenic program, namely MyoD, can associate with the deacetylase HDAC1 in vivo, and because HDACs are usually recruited to promoters by specific proteins, we considered the possibility that these two proteins might be acting together at the promoters of muscle-specific genes to repress their transcription in myoblasts. In this work, we show by chromatin immunoprecipitation (ChIP) assays that MyoD and HDAC1 are both occupying the promoter of myogenin and that this gene is in a region of repressed chromatin, as revealed by enrichment in histone H3 lysine 9 (Lys-9) methylation and the underacetylation of histones. Surprisingly, after the myoblasts are induced to differentiate, the promoter becomes absent of HDAC1, and eventually the acetyltransferase P/CAF takes it place alongside MyoD. In addition, enrichment of histone H3 acetylation (Lys-9/14) and phosphorylation of Ser-10 can now be observed at the myogenin promoter. These data strongly suggest that in addition to its widely accepted role as an activator of differentiation-specific genes, MyoD also can perform as a transcriptional repressor in proliferating myoblasts while in partnership with a HDAC.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	4
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Gene Silencing Genes, Regulator Muscle, Skeletal Growth & Development MyoD Protein Physiology Cell Differentiation Cell Line Chromatin Chemistry DNA Primers Histone Deacetylase 1 Histone Deacetylases Metabolism Cytology Genetics Myogenin Promoter Regions, Genetic Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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