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International Immunology Advance Access originally published online on January 30, 2009
International Immunology 2009 21(3):227-235; doi:10.1093/intimm/dxn143
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

The transcription repressor, ZEB1, cooperates with CtBP2 and HDAC1 to suppress IL-2 gene activation in T cells

Jun Wang, Seungsoo Lee, Charis En-Yi Teh, Karen Bunting, Lina Ma and M. Frances Shannon

Division of Molecular Bioscience, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601 Australia

Correspondence to: M. F. Shannon; E-mail: frances.shannon{at}anu.edu.au

Activation of T cells leads to the induction of many cytokine genes that are required for appropriate immune responses, including IL-2, a key cytokine for T cell proliferation and homeostasis. The activating transcription factors such as nuclear factor of activated T cells, nuclear factor {kappa}B/Rel and activated protein-1 family members that regulate inducible IL-2 gene expression have been well documented. However, negative regulation of the IL-2 gene is less studied. Here we examine the role of zinc finger E-box-binding protein (ZEB) 1, a homeodomain/Zn finger transcription factor, as a repressor of IL-2 gene transcription. We show here that ZEB1 is expressed in non-stimulated and stimulated T cells and using chromatin immunoprecipitation assays we show that ZEB1 binds to the IL-2 promoter. Over-expression of ZEB1 can repress IL-2 promoter activity, as well as endogenous IL-2 mRNA production in EL-4 T cells, and this repression is dependent on the ZEB-binding site at –100. ZEB1 cooperates with the co-repressor C-terminal-binding protein (CtBP) 2 and with histone deacetylase 1 to repress the IL-2 promoter and this cooperation depends on the ZEB-binding site in the promoter as well as the Pro-X-Asp-Leu-Ser protein–protein interaction domain in CtBP2. Thus, ZEB1 may function to recruit a repressor complex to the IL-2 promoter.

Keywords: cytokines, T cells, transcriptional regulation

Transmitting editor: A. Kelso

Received 19 September 2008, accepted 8 December 2008.


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