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

Vietor, I. et al. (2002) TIS7 interacts with the mammalian SIN3 histone deacetylase complex in epithelial cells. EMBO Journal, 21(17), pp. 4621-4631. (doi: 10.1093/emboj/cdf461) (PMID:12198164) (PMCID:PMC125408)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cotten, Professor Matthew
Authors: Vietor, I., Vadivelu, S. K., Wick, N., Hoffmann, R., Cotten, M., Seiser, C., Fialka, I., Winderlich, W., Haase, A., Kornikova, G., Brosch, G., and Huber, L. A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:EMBO Journal
Publisher:EMBO Press
ISSN:0261-4189
ISSN (Online):1460-2075

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