In:
Molecular Biology of the Cell, American Society for Cell Biology (ASCB), Vol. 24, No. 3 ( 2013-02), p. 274-284
Abstract:
Changes in the expression of potassium (K + ) channels is a pivotal event during skeletal muscle differentiation. In mouse C 2 C 12 cells, similarly to human skeletal muscle cells, myotube formation increased the expression of K v 7.1, K v 7.3, and K v 7.4, the last showing the highest degree of regulation. In C 2 C 12 cells, K v 7.4 silencing by RNA interference reduced the expression levels of differentiation markers (myogenin, myosin heavy chain, troponinT-1, and Pax3) and impaired myotube formation and multinucleation. In K v 7.4-silenced cells, the differentiation-promoting effect of the K v 7 activator N-(2-amino-4-(4-fluorobenzylamino)-phenyl)-carbamic acid ethyl ester (retigabine) was abrogated. Expression levels for the repressor element-1 silencing transcription factor (REST) declined during myotube formation. Transcript levels for K v 7.4, as well as for myogenin, troponinT-1, and Pax3, were reduced by REST overexpression and enhanced upon REST suppression by RNA interference. Four regions containing potential REST-binding sites in the 5′ untranslated region and in the first intron of the K v 7.4 gene were identified by bioinformatic analysis. Chromatin immunoprecipitation assays showed that REST binds to these regions, exhibiting a higher efficiency in myoblasts than in myotubes. These data suggest that K v 7.4 plays a permissive role in skeletal muscle differentiation and highlight REST as a crucial transcriptional regulator for this K + channel subunit.
Type of Medium:
Online Resource
ISSN:
1059-1524
,
1939-4586
DOI:
10.1091/mbc.e11-12-1044
Language:
English
Publisher:
American Society for Cell Biology (ASCB)
Publication Date:
2013
detail.hit.zdb_id:
1474922-1
SSG:
12
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