Figure 7.

Role of distinct STAT2 and/or IRF9-dependent pathways in the regulation of distinct subset of antiviral and immunoregulatory genes in response to IFNβ and TNF. Our data supports a model in which multiple pathways participate to the synergistic action of IFNβ + TNF. While the STAT1-dependent pathway, likely ISFG3, is engaged downstream of IFNβ and TNF, STAT1-independent pathways are also involved in the control of the delayed gene expression. STAT2 and IRF9 act not only in a concerted fashion, likely as a complex, but also independently. IRF9 is known to act as the DNA-binding subunit of the ISGF3 complex and therefore likely mediates binding of STAT2/IRF9 complexes and of alternative complexes devoid of STAT2. The mechanisms of STAT2-dependent regulation of gene expression remains to be characterized.