PU.1/Interferon Regulatory Factor Interactions; Mechanisms of Transcriptional Regulation

The complexity of eukaryotic gene regulation is slowly being resolved. What has become clear is that transcriptional regulation is a multi-step process that involves the assembly of macromolecular complexes. This review will discuss the biology of the ETS family transcription factor PU.1, with emphasis on its interactions with two members of the Interferon Regulatory Factor (IRF) family, interferon consensus sequence binding protein (ICSBP) and IRF-4. The role of these interactions in transcriptional regulation is discussed, with respect to DNA binding motifs, protein-protein interaction and phosphorylation states that modulate PU.1/IRF interactions. Furthermore, potential transcriptional mechanisms for several genes are discussed, focusing on genes involved in innate immunity. Data from these studies suggest at least four distinct paradigms for transcriptional regulation by an ETS protein in conjunction with either ICSBP or IRE-4. These paradigms may describe regulatory mechanisms common to many distinct transcription factor families. Last, recent data from several laboratories have now documented the expression of ICSBP and IRF-4 in a range of cell types. These data suggest that ICSBP and IRF-4 may serve functions within these cell types that are distinct from their previously recognized functions.