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PMID: 12198164 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

TIS7 interacts with the mammalian SIN3 histone deacetylase complex in epithelial cells.

The EMBO journal ·Vol. 21 ·No. 17 ·2002-09-02 ·Pages 4621-31

Vietor I, Vadivelu SK, Wick N, Hoffman R, Cotten M, Seiser C, Fialka I, Wunderlich W, Haase A, Korinkova G, Brosch G, Huber LA

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.

MeSH Terms
Amino Acid Sequence Animals Cell Line Cell Polarity DNA, Complementary/genetics Epithelial Cells/metabolism Estradiol/pharmacology Female Gene Expression Profiling HeLa Cells Histone Deacetylase 1 Histone Deacetylase 2 Histone Deacetylases/metabolism Humans Immediate-Early Proteins/metabolism Mammary Glands, Animal/cytology Membrane Proteins/metabolism Mice Molecular Sequence Data Multienzyme Complexes/metabolism Nuclear Proteins/metabolism Nuclear Receptor Co-Repressor 1 Oligonucleotide Array Sequence Analysis Protein Interaction Mapping Protein Structure, Tertiary Proto-Oncogene Proteins c-jun/physiology Recombinant Fusion Proteins/genetics,metabolism Repressor Proteins/metabolism Reverse Transcriptase Polymerase Chain Reaction Sin3 Histone Deacetylase and Corepressor Complex Transcription, Genetic
Chemicals
DNA, Complementary IFRD1 protein, human Ifrd1 protein, mouse Immediate-Early Proteins Membrane Proteins Multienzyme Complexes NCOR1 protein, human Ncor1 protein, mouse Nuclear Proteins Nuclear Receptor Co-Repressor 1 Proto-Oncogene Proteins c-jun Recombinant Fusion Proteins Repressor Proteins SAP30 protein, human Sap30 protein, mouse Estradiol HDAC1 protein, human Hdac2 protein, mouse Histone Deacetylase 1 Histone Deacetylase 2 Histone Deacetylases Sin3 Histone Deacetylase and Corepressor Complex
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Vietor Ilja
IMP, Research Institute of Molecular Pathology, Dr Bohr-Gasse 7, A-1030 Vienna, Austria.
Vadivelu Santhosh K
Wick Nikolaus
Hoffman Robert
Cotten Matt
Seiser Christian
Fialka Irene
Wunderlich Winfried
Haase Astrid
Korinkova Gabriela
Brosch Gerald
Huber Lukas A
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdf461
Published
2002-09-02
Pages
4621-31
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125408
Subset
IM
Databases
GENBANK
X17400
External Links
PubMed source DOI: 10.1093/emboj/cdf461 PMC Full Text View journal details
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