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PAK1 and CtBP1 Regulate the Coupling of Neuronal Activity to Muscle Chromatin and Gene Expression.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2015 Dec; Vol. 35 (24), pp. 4110-20. Date of Electronic Publication: 2015 Sep 28. - Publication Year :
- 2015
-
Abstract
- Acetylcholine receptor (AChR) expression in innervated muscle is limited to the synaptic region. Neuron-induced electrical activity participates in this compartmentalization by promoting the repression of AChR expression in the extrasynaptic regions. Here, we show that the corepressor CtBP1 (C-terminal binding protein 1) is present on the myogenin promoter together with repressive histone marks. shRNA-mediated downregulation of CtBP1 expression is sufficient to derepress myogenin and AChR expression in innervated muscle. Upon denervation, CtBP1 is displaced from the myogenin promoter and relocates to the cytoplasm, while repressive histone marks are replaced by activating ones concomitantly to the activation of myogenin expression. We also observed that upon denervation the p21-activated kinase 1 (PAK1) expression is upregulated, suggesting that phosphorylation by PAK1 may be involved in the relocation of CtBP1. Indeed, preventing CtBP1 Ser158 phosphorylation induces CtBP1 accumulation in the nuclei and abrogates the activation of myogenin and AChR expression. Altogether, these findings reveal a molecular mechanism to account for the coordinated control of chromatin modifications and muscle gene expression by presynaptic neurons via a PAK1/CtBP1 pathway.<br /> (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Subjects :
- Active Transport, Cell Nucleus genetics
Alcohol Oxidoreductases genetics
Animals
Cell Nucleus metabolism
Chromatin genetics
Chromatin metabolism
Cytoplasm metabolism
DNA-Binding Proteins genetics
Histones genetics
Histones metabolism
Mice
Muscle, Skeletal metabolism
Myogenin genetics
Phosphorylation
Promoter Regions, Genetic genetics
RNA Interference
RNA, Small Interfering
Receptors, Cholinergic genetics
Receptors, Cholinergic metabolism
Transcriptional Activation genetics
Up-Regulation
p21-Activated Kinases biosynthesis
p21-Activated Kinases genetics
Alcohol Oxidoreductases metabolism
DNA-Binding Proteins metabolism
Muscle Denervation
Muscle, Skeletal innervation
Myogenin biosynthesis
p21-Activated Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5549
- Volume :
- 35
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 26416879
- Full Text :
- https://doi.org/10.1128/MCB.00354-15