TIS7 interacts with the mammalian SIN3 histone deacetylase complex in epithelial cells.
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.
Mesh Terms:
Amino Acid Sequence, Animals, Cell Line, Cell Polarity, DNA, Complementary, Epithelial Cells, Estradiol, Female, Gene Expression Profiling, Hela Cells, Histone Deacetylase 1, Histone Deacetylase 2, Histone Deacetylases, Humans, Immediate-Early Proteins, Mammary Glands, Animal, Membrane Proteins, Mice, Molecular Sequence Data, Multienzyme Complexes, Nuclear Proteins, Nuclear Receptor Co-Repressor 1, Oligonucleotide Array Sequence Analysis, Protein Interaction Mapping, Protein Structure, Tertiary, Proto-Oncogene Proteins c-jun, Recombinant Fusion Proteins, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, Sin3 Histone Deacetylase and Corepressor Complex, Transcription, Genetic
Amino Acid Sequence, Animals, Cell Line, Cell Polarity, DNA, Complementary, Epithelial Cells, Estradiol, Female, Gene Expression Profiling, Hela Cells, Histone Deacetylase 1, Histone Deacetylase 2, Histone Deacetylases, Humans, Immediate-Early Proteins, Mammary Glands, Animal, Membrane Proteins, Mice, Molecular Sequence Data, Multienzyme Complexes, Nuclear Proteins, Nuclear Receptor Co-Repressor 1, Oligonucleotide Array Sequence Analysis, Protein Interaction Mapping, Protein Structure, Tertiary, Proto-Oncogene Proteins c-jun, Recombinant Fusion Proteins, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, Sin3 Histone Deacetylase and Corepressor Complex, Transcription, Genetic
EMBO J.
Date: Sep. 02, 2002
PubMed ID: 12198164
View in: Pubmed Google Scholar
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