| RRC ID |
1227
|
| 著者 |
Funato N, Ohyama K, Kuroda T, Nakamura M.
|
| タイトル |
Basic helix-loop-helix transcription factor epicardin/capsulin/Pod-1 suppresses differentiation by negative regulation of transcription.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
Epicardin/capsulin/Pod-1, expressed in skeletal myoblasts within brachial arches and in the condensing mesenchyme, is a member of the basic helix-loop-helix (bHLH) transcription factor family that is involved in various cell differentiation processes. In this study, we examined the functional properties of epicardin/capsulin/Pod-1 in differentiation. The yeast and mammalian two-hybrid systems showed physical associations between epicardin/capsulin/Pod-1 and E2A, both of which were present in the nuclei. The bHLH domains mediated this association. Ectopic expression of epicardin/capsulin/Pod-1 inhibited E2A-dependent activation of the exogenous and endogenous expression of the cyclin-dependent kinase inhibitor, p21(WAF1/Cip1) gene, and the muscle creatine kinase gene that encodes the predominant creatine kinase isoform expressed in mammalian skeletal muscle. Transfection with epicardin/capsulin/Pod-1 small interfering RNA abolished the epicardin/capsulin/Pod-1-mediated suppression of E12-dependent activation of the p21 promoter. Chromatin immunoprecipitation assay showed that epicardin/capsulin/Pod-1 was physically associated with the muscle creatine kinase promoter in vivo. Moreover, terminal differentiation of C2C12 myoblasts was inhibited by exogenous introduction of epicardin/capsulin/Pod-1. These inhibitory functions of epicardin/capsulin/Pod-1 closely resemble those of the bHLH inhibitor Twist protein. These results indicate that epicardin/capsulin/Pod-1 functions as a negative regulator of differentiation of myoblasts through transcription in at least two distinct steps, cell growth arrest and lineage-specific differentiation.
|
| 巻・号 |
278(9)
|
| ページ |
7486-93
|
| 公開日 |
2003-2-28
|
| DOI |
10.1074/jbc.M212248200
|
| PII |
S0021-9258(19)32689-4
|
| PMID |
12493738
|
| MeSH |
Animals
Basic Helix-Loop-Helix Transcription Factors
Cell Differentiation
Cell Line
Cell Lineage
Cell Nucleus / metabolism
Chromatin / metabolism
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / metabolism
Humans
Immunoblotting
Luciferases / metabolism
Mice
Microscopy, Fluorescence
Muscles / cytology
Plasmids / metabolism
Precipitin Tests
Promoter Regions, Genetic
Protein Binding
RNA, Small Interfering / metabolism
Transcription Factors / physiology*
Transcription, Genetic*
Transcriptional Activation
Transfection
Tumor Cells, Cultured
Two-Hybrid System Techniques
|
| IF |
4.238
|
| 引用数 |
44
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
C2C12(RCB0987)
10T1/2(RCB0247) |
