| First Author | Kokura K | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 36 | Pages | 34115-21 |
| PubMed ID | 11441023 | Mgi Jnum | J:159081 |
| Mgi Id | MGI:4441140 | Doi | 10.1074/jbc.M105747200 |
| Citation | Kokura K, et al. (2001) The Ski protein family is required for MeCP2-mediated transcriptional repression. J Biol Chem 276(36):34115-21 |
| abstractText | DNA methylation is essential for development in the mouse and plays an important role in inactivation of the X chromosome and genomic imprinting. MeCP2 is the founder member of a family of methyl-CpG-binding proteins. MeCP2 directly binds to the co-repressor mSin3, which interacts with class I histone deacetylase, recruiting them to methyl-CpG regions to suppress transcription. Here, we report that MeCP2 directly binds to two co-repressors, c-Ski and N-CoR, in addition to mSin3A, and that the c-Ski, which is encoded by the c-ski proto-onocogene, is required for MeCP2-mediated transcriptional repression. The two regions of c-Ski, including the C-terminal coiled-coil region, interact with the transcriptional repression domain in the center of the MeCP2 molecule. The immunostaining signals for c-Ski and MeCP2 overlap in the nuclear heterochromatin region, suggesting the co-localization of the two proteins. The degree of transcriptional repression mediated by a Gal4-MeCP2 fusion protein was abrogated by overexpression of the putative dominant negative form of c-Ski. Furthermore, injection of antibodies against c-Ski and Sno almost completely abolished the transcriptional repression mediated by the Gal4-MeCP2 fusion protein. These results suggest that the ski gene family is involved in methyl CpG-mediated transcriptional repression. |
