Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation*
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Genes, MHC Class II*
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Humans
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Interferon Regulatory Factor-1
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Interferon-gamma / pharmacology*
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Leucine Zippers
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Mice
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Models, Genetic
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Nuclear Proteins*
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Phosphoproteins / metabolism
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Promoter Regions, Genetic
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Protein Binding
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Rabbits
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STAT1 Transcription Factor
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Signal Transduction
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Trans-Activators / biosynthesis*
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors / metabolism*
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Transcriptional Activation
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Upstream Stimulatory Factors
Substances
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DNA-Binding Proteins
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IRF1 protein, human
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Interferon Regulatory Factor-1
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Irf1 protein, mouse
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MHC class II transactivator protein
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Nuclear Proteins
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Phosphoproteins
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STAT1 Transcription Factor
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STAT1 protein, human
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Stat1 protein, mouse
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Trans-Activators
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Transcription Factors
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USF1 protein, human
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Upstream Stimulatory Factors
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Usf1 protein, mouse
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Interferon-gamma