By Underwood J.L.
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30 HMG I1Y is essential for the inducible expression of class II genes and may be important for B cell-specific expression as well. HMG I1Y does not function as a classical transcriptional activator, rather it serves as a cofactor for traditional activators. HMG I1Y may function by facilitating the assembly of an active transcription complex, since it can bend DNA as well as facilitate the interaction of activators with their binding sites. The role of HMG I/Y in transcription factor loading is exemplified by its involvement in the regulation of IFN-~ gene expression.
The wild-type counterparts of the mutated genes in two groups of patients have been identified by complementation cloning (achieved by gene transfer of cDNA expression vectors containing side-selected cDNAs from class II positive B lymphocytes). The defect in complementation group 4 involves an X-box binding protein designated RFX-5 and the defective protein in complementation group 2 affects what appears to be a potent transactivator of class II MHC genes designated CIIT A (see below). This protein does not appear to be a traditional DNA-binding protein.
The levels of YB-l are inversely related to the levels of MHC class II gene expression and the overexpression of YB-l can repress y-interferon induced activation of class II genes. The X box is further subdivisible into an upstream Xl box and a downstream X2 box, which interact with distinct transcription factors. 21 The most recently cloned of these factors, RFX5, has been shown to be the factor mutated in cases of BLS belonging to complementation group C, in which there is a defect in the binding of RFX.