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Ski co-repressor complexes maintain the basal repressed state of the TGF-beta target gene, SMAD7, via HDAC3 and PRMT5.
- Source :
-
Genes to cells : devoted to molecular & cellular mechanisms [Genes Cells] 2009 Jan; Vol. 14 (1), pp. 17-28. Date of Electronic Publication: 2008 Nov 21. - Publication Year :
- 2009
-
Abstract
- The products encoded by ski and its related gene, sno, (Ski and Sno) act as transcriptional co-repressors and interact with other co-repressors such as N-CoR/SMRT and mSin3A. Ski and Sno mediate transcriptional repression by various repressors, including Mad, Rb and Gli3. Ski/Sno also suppress transcription induced by multiple activators, such as Smads and c-Myb. In particular, the inhibition of TGF-beta-induced transcription by binding to Smads is correlated with the oncogenic activity of Ski and Sno. However, the molecular mechanism by which Ski and Sno mediate transcriptional repression remains unknown. In this study, we report the purification and characterization of Ski complexes. The Ski complexes purified from HeLa cells contained histone deacetylase 3 (HDAC3) and protein arginine methyltransferase 5 (PRMT5), in addition to multiple Smad proteins (Smad2, Smad3 and Smad4). Chromatin immunoprecipitation assays indicated that these components of the Ski complexes were localized on the SMAD7 gene promoter, which is the TGF-beta target gene, in TGF-beta-untreated HepG2 cells. Knockdown of these components using siRNA led to up-regulation of SMAD7 mRNA. These results indicate that Ski complexes serve to maintain a TGF-beta-responsive promoter at a repressed basal level via the activities of histone deacetylase and histone arginine methyltransferase.
- Subjects :
- Cell Cycle Proteins metabolism
Chromatin Immunoprecipitation
DNA-Binding Proteins isolation & purification
HeLa Cells
Humans
Multiprotein Complexes isolation & purification
Multiprotein Complexes metabolism
Nuclear Proteins metabolism
Promoter Regions, Genetic
Protein Transport drug effects
Protein-Arginine N-Methyltransferases
Proto-Oncogene Proteins isolation & purification
Smad4 Protein metabolism
Sodium Chloride pharmacology
Transcription, Genetic drug effects
DNA-Binding Proteins metabolism
Histone Deacetylases metabolism
Protein Methyltransferases metabolism
Proto-Oncogene Proteins metabolism
Repressor Proteins metabolism
Smad7 Protein genetics
Transforming Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2443
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Genes to cells : devoted to molecular & cellular mechanisms
- Publication Type :
- Academic Journal
- Accession number :
- 19032343
- Full Text :
- https://doi.org/10.1111/j.1365-2443.2008.01246.x