Histone Deacetylase 9 couples neuronal activity to muscle chromatin acetylation and gene expression - ENS de Lyon - École normale supérieure de Lyon Access content directly
Journal Articles Nature Neuroscience Year : 2005

Histone Deacetylase 9 couples neuronal activity to muscle chromatin acetylation and gene expression

Abstract

Electrical activity arising from motor innervation influences skeletal muscle physiology by controlling the expression of many muscle genes, including acetylcholine receptor (AChR) subunits genes. How electrical activity is converted into a transcriptional response remains largely unknown. We show that motor innervation controls chromatin acetylation in skeletal muscle and that histone deacetylase 9 (HDAC9) is a signal-responsive transcriptional repressor, which is down-regulated upon denervation, with consequent up-regulation of chromatin acetylation and AChR expression. Forced expression of HDAC9 in denervated muscle prevents up-regulation of activity-dependent genes and chromatin acetylation by linking MEF2 and class I HDACs. Conversely, HDAC9 null mice are supersensitive to denervation-induced changes in gene expression and display chromatin hyperacetylation, and delayed perinatal downregulation of myogenin, an activator of AChR genes. These findings reveal a molecular mechanism to account for the control of chromatin acetylation by presynaptic neurons and activity-dependent regulation of skeletal muscle genes by motor innervation.
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Dates and versions

ensl-00182187 , version 1 (11-12-2007)

Identifiers

  • HAL Id : ensl-00182187 , version 1
  • PRODINRA : 251045

Cite

Alexandre Mejat, Francis Ramond, Rhonda Bassel Duby, Saadi Khochbin, Eric N Olson, et al.. Histone Deacetylase 9 couples neuronal activity to muscle chromatin acetylation and gene expression. Nature Neuroscience, 2005, 8 (3), pp.313-321. ⟨ensl-00182187⟩
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