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

Alexandre Mejat 1 Francis Ramond 1 Rhonda Bassel Duby 2 Saadi Khochbin 3 Eric N Olson 2 Laurent Schaeffer 1, *
* Corresponding author
1 LBMC - Laboratoire de Biologie Moléculaire de la Cellule
2 UTSW at Dallas
3 IAB
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.
Keywords : muscle neuron chromatin histone deacetylases electrical activity
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Journal articles
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https://hal-ens-lyon.archives-ouvertes.fr/ensl-00182187
Contributor : Laurent Schaeffer <>
Submitted on : Tuesday, December 11, 2007 - 2:50:29 PM
Last modification on : Thursday, February 7, 2019 - 4:10:35 PM

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  • HAL Id : ensl-00182187, version 1

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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, Nature Publishing Group, 2005, 8 (3), pp.313-321. ⟨ensl-00182187⟩

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