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.
Vietor
Ilja
I
IMP, Research Institute of Molecular Pathology, Dr Bohr-Gasse 7, A-1030 Vienna, Austria.
Vadivelu
Santhosh K
SK
Wick
Nikolaus
N
Hoffman
Robert
R
Cotten
Matt
M
Seiser
Christian
C
Fialka
Irene
I
Wunderlich
Winfried
W
Haase
Astrid
A
Korinkova
Gabriela
G
Brosch
Gerald
G
Huber
Lukas A
LA
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D018076:DNA, Complementary / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D006367:HeLa Cells; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000166:cytology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1; D020411:Oligonucleotide Array Sequence Analysis; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic
D018076:DNA, Complementary; C490045:IFRD1 protein, human; C490044:Ifrd1 protein, mouse; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D009097:Multienzyme Complexes; C539127:NCOR1 protein, human; C539128:Ncor1 protein, mouse; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C113294:SAP30 protein, human; C491870:Sap30 protein, mouse; D004958:Estradiol; C110550:HDAC1 protein, human; C533424:Hdac2 protein, mouse; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex