Regulation of cooperative function of the Il12b enhancer and promoter by the interferon regulatory factors 3 and 5

► We found that interferon regulatory factor three (IRF3) and five bind to enhancer of the Il12b gene. ► We identified two interferon stimulated response elements (ISREs) on enhancer of the Il12b gene. ► IRF5 mediates cooperativity of the enhancer with the promoter that also contains ISREs. ► IRF3 binding to the enhancer and promoter causes suppression of the gene activation. ► We show that 5′ sequence of the enhancer and promoter ISREs critically affect the function of IRF3.