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Transcriptional repression of the IL-2 gene in Th cells by ZEB
D H Yasui1, T Genetta, T Kadesch
1Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
Th1- and Th2-type cells mediate distinct effector functions via cytokine secretion in response to immunologic challenge. Precursor Th cells transcribe IFN-gamma, IL-2, and IL-4 upon activation. Repeated stimulation of Th precursor cells in the presence of IL-4 leads to terminally differentiated Th2 cells that have lost the ability to transcribe the IL-2 gene. We provide evidence that repression of IL-2 gene expression in Th2 cells and partial repression in Th1 cells are mediated by ZEB, a zinc finger, E box-binding transcription factor. This factor binds to a negative regulatory element, NRE-A, in the IL-2 promoter, thereby acting as a potent repressor of IL-2 transcription.
Th1- and Th2-type cells mediate distinct effector functions via cytokine secretion in response to immunologic challenge. Precursor Th cells transcribe IFN-gamma, IL-2, and IL-4 upon activation. Repeated stimulation of Th precursor cells in the presence of IL-4 leads to terminally differentiated Th2 cells that have lost the ability to transcribe the IL-2 gene. We provide evidence that repression of IL-2 gene expression in Th2 cells and partial repression in Th1 cells are mediated by ZEB, a zinc finger, E box-binding transcription factor. This factor binds to a negative regulatory element, NRE-A, in the IL-2 promoter, thereby acting as a potent repressor of IL-2 transcription.