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Figure 3. Schematic diagram of proposed model of IFN-ß-induced CD40 gene expression. IFN-ß activates JAK-STAT-1
pathway (30 min to 2 h); STAT-1 then dimerizes, translocates into the nucleus, and binds to GAS elements in the CD40 promoter. Concurrent with STAT-1 recruitment, IFN-ß leads to modifications in H3 and H4 and recruitment of RNA Pol II. IFN-ß also transiently induces the expression of SOCS-1 (mRNA between 1 to 4 h; protein between 1 to 8 h), which binds to activated JAK1 and inhibits its catalytic activity, subsequently inhibiting STAT-1 activation. Inhibition of STAT-1 activation by SOCS-1 results in a reduction of IFN-ß-induced CD40 gene expression.
