Postsynaptic chromatin is under neural control at the neuromuscular junction.
In adult skeletal muscle, the nicotinic acetylcholine receptor (AChR) specifically accumulates at the neuromuscular junction, to allow neurotransmission. This clustering is paralleled by a compartmentalization of AChR genes expression to subsynaptic nuclei, which acquire a unique gene expression program and a specific morphology in response to neural cues. Our results demonstrate that neural agrin-dependent reprogramming of myonuclei involves chromatin remodelling, histone hyperacetylation and histone hyperphosphorylation. Activation of AChR genes in subsynaptic nuclei is mediated by the transcription factor GABP. Here we demonstrate that upon activation, GABP recruits the histone acetyl transferase (HAT) p300 on the AChR epsilon subunit promoter, whereas it rather recruits the histone deacetylase HDAC1 when the promoter is not activated. Moreover, the HAT activity of p300 is required in vivo for AChR expression. GABP therefore couples chromatin hyperacetylation and AChR activation by neural factors in subsynaptic nuclei.
Ravel-Chapuis
Aymeric
A
Equipe Différenciation Neuromusculaire, IFR128, UMR5161, CNRS, INRA, Université de Lyon, Lyon Cedex, France.
Vandromme
Marie
M
Thomas
Jean-Luc
JL
Schaeffer
Laurent
L
D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D018274:Electroporation; D005455:Fluorescent Antibody Technique; D051268:GA-Binding Protein Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009435:Synaptic Transmission / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D018797:Cell Cycle Proteins; D017931:DNA Primers; D051268:GA-Binding Protein Transcription Factor; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D006657:Histones; D008156:Luciferases; D011978:Receptors, Nicotinic; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor