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PMID:11441023

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Citation

Kokura, K, Kaul, SC, Wadhwa, R, Nomura, T, Khan, MM, Shinagawa, T, Yasukawa, T, Colmenares, C and Ishii, S (2001) The Ski protein family is required for MeCP2-mediated transcriptional repression. J. Biol. Chem. 276:34115-21

Abstract

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.

Links

PubMed Online version:10.1074/jbc.M105747200

Keywords

Blotting, Western; Cell Line; Cell Nucleus/metabolism; Chromosomal Proteins, Non-Histone; CpG Islands; DNA Methylation; DNA, Complementary/metabolism; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/metabolism; Gene Expression Regulation; Genes, Dominant; Glutathione Transferase/metabolism; Heterochromatin/chemistry; Humans; Methyl-CpG-Binding Protein 2; Multigene Family; Precipitin Tests; Protein Binding; Protein Structure, Tertiary; Proto-Oncogene Proteins/chemistry; Proto-Oncogene Proteins/metabolism; Recombinant Fusion Proteins/chemistry; Repressor Proteins; Transcription, Genetic

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:SKI

enables

GO:0019904: protein domain specific binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P51608

F

Seeded From UniProt

complete

HUMAN:MECP2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MECP2

located_in

GO:0000792: heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:NCOR1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P51608

F

Seeded From UniProt

complete

HUMAN:MECP2

enables

GO:0047485: protein N-terminus binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q60974

F

Seeded From UniProt

complete

HUMAN:MECP2

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MECP2

enables

GO:0019904: protein domain specific binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P12755

F

Seeded From UniProt

complete

HUMAN:MECP2

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MECP2

part_of

GO:0000792: heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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