Heregulin-induced epigenetic regulation of the utrophin-A promoter
- 作者：Utpal Basu ; Mads Gyrd-Hansen ; Santhosh M. Baby ; Olga Lozynska ; Thomas O.B. Krag ; Claus J. Jensen ; Morten Frö ; din ; Tejvir S. Khurana
- 关键词：Utrophin ; Heregulin ; MSK1/2 ; Chromatin remodeling ; Transcription
- 刊名：FEBS Letters
- 出版年：2007
- 期刊代码：70_00145793
- 类别：bio
- 出版时间：4 September 2007
- 卷：581
- 期：22
- 页码：4153-4158
- 文件大小：839 K
摘要
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.