Activation of the MHC class II transactivator CIITA by interferon-gamma requires cooperative interaction between Stat1 and USF-1

Immunity. 1998 Feb;8(2):157-66. doi: 10.1016/s1074-7613(00)80468-9.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation*
  • Genes, MHC Class II*
  • Humans
  • Interferon Regulatory Factor-1
  • Interferon-gamma / pharmacology*
  • Leucine Zippers
  • Mice
  • Models, Genetic
  • Nuclear Proteins*
  • Phosphoproteins / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Rabbits
  • STAT1 Transcription Factor
  • Signal Transduction
  • Trans-Activators / biosynthesis*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Upstream Stimulatory Factors


  • DNA-Binding Proteins
  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • Irf1 protein, mouse
  • MHC class II transactivator protein
  • Nuclear Proteins
  • Phosphoproteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Stat1 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • USF1 protein, human
  • Upstream Stimulatory Factors
  • Usf1 protein, mouse
  • Interferon-gamma