The role of IRF-4 in transcriptional regulation

Gene expression is a tightly regulated process involving multiple levels of control spanning histone acetylation to protein turnover. One of the first events in this cascade is transcription, which itself is a multistep process involving protein-protein interaction and macromolecular assembly. Here we review the role of the interferon (IFN) regulatory factor (IRF) transcription factor family member IRF-4 in transcriptional regulation. IRF-4 was initially characterized in lymphocytes and was shown to function as both a transcriptional repressor and activator. More recently, IRF-4 expression and function have been reported in macrophages. The ability of IRF-4 to serve as both a transcriptional activator and repressor is determined, in part, by binding to distinct DNA-binding motifs and through interaction with various additional transcription factors, most notably with the Ets family member PU.1. The details governing these functional differences are the focus of this review. Importantly, the role of posttranslational modification and nuclear translocation of IRF-4 in transcriptional regulation are addressed. Several possible paradigms of transcriptional regulation by IRF-4 are proposed, where these paradigms may describe regulatory mechanisms common to many distinct transcription factor families.