Muhlethaler-Mottet A, Di Berardino W, Otten L A, Mach B
Louis Jeantet Laboratory of Molecular Genetics, Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
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.
CIITA是γ干扰素（IFNγ）诱导MHC II类基因表达的介质。CIITA基因本身通过其四个启动子之一（PIV）被选择性激活。我们在此表明，三个顺式作用元件，即GAS、E盒和IRF-1结合位点，以及反式作用因子Stat1和IRF-1，对于IFNγ激活CIITA启动子IV至关重要。Stat1仅在普遍存在的因子USF-1存在时才与GAS位点结合，而USF-1与相邻的E盒结合。实际上，Stat1和USF-1以协同方式结合到GAS/E盒基序上。因此，IFNγ激活CIITA的特异性由GAS/E盒基序以及IFNγ激活的Stat1和USF-1的选择性相互作用所决定。这阐明了IFNγ激活MHC-II表达的整个途径中缺失的环节。
