Activation of the MHC class II transactivator CIITA by interferon-gamma requires cooperative interaction between Stat1 and USF-1.
CIITA is the mediator of MHC class II gene induction by interferon-gamma (IFNgamma). The CIITA gene is itself selectively activated via one of its four promoters (PIV). We show here that three cis-acting elements, the GAS, the E box, and the IRF-1-binding site, as well as the transacting factors Stat1 and IRF-1, are essential for activation of CIITA promoter IV by IFNgamma. Stat1 binds to the GAS site only in the presence of the ubiquitous factor USF-1, which binds to the adjacent E box. Indeed, Stat1 and USF-1 bind to the GAS/E box motif in a cooperative manner. The specificity for CIITA activation by IFNgamma is thus dictated by the GAS/E box motif and by the selective interaction of IFNgamma-activated Stat1 and USF-1. This clarifies the missing link in the overall pathway of IFNgamma activation of MHC-II expression.
Muhlethaler-Mottet
A
A
Louis Jeantet Laboratory of Molecular Genetics, Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
Di Berardino
W
W
Otten
L A
LA
Mach
B
B
D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology*; D016350:Leucine Zippers; D051379:Mice; D008957:Models, Genetic; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011817:Rabbits; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D010750:Phosphoproteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; D007371:Interferon-gamma