A minimal IFN-gamma promoter confers Th1 selective expression.
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.
Soutto
Mohammed
M
Division of Rheumatology, Department of Medicine, Vanderbilt University School of Medicine, Medical Center North T3219, 21st and Garland, Nashville, TN 37232, USA.
Zhang
Feng
F
Enerson
Ben
B
Tong
Yingkai
Y
Boothby
Mark
M
Aune
Thomas M
TM
D020121:5' Untranslated Regions / Q000276:immunology; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D050981:Erythroid-Specific DNA-Binding Factors; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D019169:Jurkat Cells; D020935:MAP Kinase Signaling System / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D020218:Response Elements / Q000276:immunology; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology; D050986:YY1 Transcription Factor; D048051:p38 Mitogen-Activated Protein Kinases; D000098815:T-bet Transcription Factor
D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D050986:YY1 Transcription Factor; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases