A Minimal IFN-γ Promoter Confers Th1 Selective Expression

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Abstract
Th1 and Th2 cells differentiate from naive precursors to effector cells that produce either IFN-γ or IL-4, respectively. To identify transcriptional paths leading to activation and silencing of the IFN-γ gene, we analyzed transgenic mice that express a reporter gene under the control of the 5′ IFN-γ promoter. We found that as the length of the promoter is increased, −110 to −225 to −565 bp, the activity of the promoter undergoes a transition from Th1 nonselective to Th1 selective. This is due, at least in part, to a T box expressed in T cells-responsive unit within the −565 to −410 region of the IFN-γ promoter. The −225 promoter is silent when compared with the −110 promoter and silencing correlates with Yin Yang 1 binding to the promoter. The p38 mitogen-activated protein kinase signaling pathway, which also regulates IFN-γ gene transcription, regulates the −70- to −44-bp promoter element. Together, the results demonstrate that a minimal IFN-γ promoter contains a T box expressed in T cells responsive unit and is sufficient to confer Th1 selective expression upon a reporter.