Heregulin-induced Epigenetic Regulation of the Utrophin-a Promoter.
From: Department of Physiology & Pennsylvania Muscle Institute, 3700 Hamilton Walk, University of Pennsylvania, Philadelphia, PA 19104-6085, USA.
FEBS letters
- Publish Date: Sep 2007
- ISSN: 0014-5793
- Volume: 581
- Issue: 22
- Pages: 4153-8
- Medium: Print
- Language: English
- Citation (JAMA): Basu Utpal, Gyrd-Hansen Mads, Baby Santhosh M, et al. Heregulin-induced Epigenetic Regulation of the Utrophin-a Promoter.. FEBS Lett. Sep 2007;581:4153-8
Abstract
Utrophin is the autosomal homolog of dystrophin, the product of the Duchenne’s muscular dystrophy (DMD) locus. Utrophin is of therapeutic interest since its over-expression can compensate dystrophin’s absence. Utrophin is enriched at neuromuscular junctions due to heregulin-mediated utrophin-A promoter activation. We demonstrate that heregulin activated MSK1/2 and phosphorylated histone H3 at serine 10 in cultured C2C12 muscle cells, in an ERK-dependent manner. MSK1/2 inhibition suppressed heregulin-mediated utrophin-A activation. MSK1 over-expression potentiated heregulin-mediated utrophin-A activation and chromatin remodeling at the utrophin-A promoter. These results identify MSK1/2 as key effectors modulating utrophin-A expression as well as identify novel targets for DMD therapy.
Mesh Headings (Keywords): Animals, Cells, Cultured, Chromatin Assembly and Disassembly, Enzyme Activation, Epigenesis, Genetic, Histones, Mice, Models, Genetic, Muscle Cells, Neuregulin-1, Phosphorylation, Promoter Regions (Genetics), Ribosomal Protein S6 Kinases, 90-kDa, Utrophin
Check for Full Text / PubMed Unique Identifier (PMID): 17692845
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