Heregulin-induced epigenetic regulation of the utrophin-A promoter.

Journal article

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.

Authors: Basu, U; Gyrd-Hansen, M; Baby, S; Lozynska, O; Krag, T

• Journal: FEBS letters
• Volume: 581
• Issue: 22
• Pages: 4153-4158
• Publication date: 2007-09-01
• DOI: 10.1016/j.febslet.2007.07.021
• EISSN: 1873-3468
• ISSN: 0014-5793
• Language: English
• Keywords: Ribosomal Protein S6 Kinases, 90-kDa; Promoter Regions, Genetic; Cells, Cultured; Neuregulin-1; Muscle Cells; Mice; Animals; Enzyme Activation; Phosphorylation; Epigenesis, Genetic; Chromatin Assembly and Disassembly; Models, Genetic; Histones; Utrophin