The Ski protein family is required for MeCP2-mediated transcriptional repression.

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.
Mesh Terms:
Blotting, Western, Cell Line, Cell Nucleus, Chromosomal Proteins, Non-Histone, CpG Islands, DNA Methylation, DNA, Complementary, DNA-Binding Proteins, Gene Expression Regulation, Genes, Dominant, Glutathione Transferase, Heterochromatin, Humans, Methyl-CpG-Binding Protein 2, Multigene Family, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Repressor Proteins, Transcription, Genetic
J. Biol. Chem.
Date: Sep. 07, 2001
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