Abstract
The mammalian SIN3 complex consists of histone deacetylases (HDAC1, HDAC2), several known proteins (SAP30, N-CoR) and as yet unidentified proteins. Here we show that the mouse tetradecanoyl phorbol acetate induced sequence 7 (TIS7) protein is a novel transcriptional co-repressor that can associate with the SIN3 complex. We have identified tis7 as a gene that is up-regulated upon loss of polarity in a mouse mammary gland epithelial cell line expressing an estrogen-inducible c-JunER fusion protein. In unpolarized cells, TIS7 protein levels increase and TIS7 translocates into the nucleus. Overexpression of tis7 causes loss of polarity and represses a set of genes, as revealed by cDNA microarray analysis. We have shown that TIS7 protein interacts with several proteins of the SIN3 complex (mSin3B, HDAC1, N-CoR and SAP30) by yeast two-hybrid screening and co-immunoprecipitations. TIS7 co-immunoprecipitated HDAC complex is enzymatically active and represses a GAL4-dependent reporter transcription. The transcriptional repression of endogenous genes by tis7 overexpression is HDAC dependent. Thus, we propose TIS7 as a transcriptional co-repressor affecting the expression of specific genes in a HDAC activity-dependent manner during cell fate decisions, e.g. scattering.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Line
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Cell Polarity
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DNA, Complementary / genetics
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Epithelial Cells / metabolism*
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Estradiol / pharmacology
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Female
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Gene Expression Profiling
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HeLa Cells
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Histone Deacetylase 1
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Histone Deacetylase 2
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Histone Deacetylases / metabolism*
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Humans
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Immediate-Early Proteins / metabolism*
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Mammary Glands, Animal / cytology
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Membrane Proteins / metabolism*
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Mice
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Molecular Sequence Data
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Multienzyme Complexes / metabolism*
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Nuclear Proteins / metabolism
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Nuclear Receptor Co-Repressor 1
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Oligonucleotide Array Sequence Analysis
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Protein Interaction Mapping
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-jun / physiology
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Sin3 Histone Deacetylase and Corepressor Complex
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Transcription, Genetic
Substances
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DNA, Complementary
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IFRD1 protein, human
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Ifrd1 protein, mouse
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Immediate-Early Proteins
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Membrane Proteins
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Multienzyme Complexes
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NCOR1 protein, human
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Ncor1 protein, mouse
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Nuclear Proteins
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Nuclear Receptor Co-Repressor 1
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Proto-Oncogene Proteins c-jun
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Recombinant Fusion Proteins
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Repressor Proteins
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SAP30 protein, human
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Sap30 protein, mouse
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Estradiol
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HDAC1 protein, human
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Hdac2 protein, mouse
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Histone Deacetylase 1
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Histone Deacetylase 2
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Histone Deacetylases
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Sin3 Histone Deacetylase and Corepressor Complex