A minimal IFN-gamma promoter confers Th1 selective expression.

Soutto M, Zhang F, Enerson B, Tong Y, Boothby M, Aune TM
J Immunol. 2002 169 (8): 4205-12

PMID: 12370350 · DOI:10.4049/jimmunol.169.8.4205

Th1 and Th2 cells differentiate from naive precursors to effector cells that produce either IFN-gamma or IL-4, respectively. To identify transcriptional paths leading to activation and silencing of the IFN-gamma gene, we analyzed transgenic mice that express a reporter gene under the control of the 5' IFN-gamma 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-gamma 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-gamma gene transcription, regulates the -70- to -44-bp promoter element. Together, the results demonstrate that a minimal IFN-gamma promoter contains a T box expressed in T cells responsive unit and is sufficient to confer Th1 selective expression upon a reporter.

MeSH Terms (24)

5' Untranslated Regions Animals Base Sequence Cells, Cultured DNA-Binding Proteins Erythroid-Specific DNA-Binding Factors Gene Expression Regulation Humans Interferon-gamma Jurkat Cells MAP Kinase Signaling System Mice Mice, Transgenic Mitogen-Activated Protein Kinases Molecular Sequence Data p38 Mitogen-Activated Protein Kinases Promoter Regions, Genetic Protein Binding Response Elements T-Box Domain Proteins Th1 Cells Trans-Activators Transcription Factors YY1 Transcription Factor

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