The related transcription factors IRF4 and IRF8 regulate key processes in DCs, B cells and T cells, yet both have weak DNA-binding activity and thus must interact with other factors. In Nature and Science, Murphy, Leonard and Singh show that BATF proteins, a family of AP-1-like transcription factors, recruit IRF4 and IRF8 to DNA-binding sites (AICE motifs) in T cells and DCs. Motif-discovery analyses identify two composite elements that differ only by spacing between the half-sites. Both BATF and IRF4 are needed to drive high expression of Il17, Il10 and Ctla4 in T cells. BATF expression, induced by IFN-γ during infection, can rescue the development of CD8α+ and CD103+ DCs in BATF3-deficient mice. The leucine-zipper domain of BATF proteins is necessary for interaction with IRF4, as substitution of His55 impairs the BATF-IRF4 interaction. These findings show how distinct gene-expression programs can be turned on through the recognition of composite sites.

Nature (13 September 2012) doi:10.1038/nature11530 & doi:10.1038/nature11531 & Science (9 September 2012) doi:10.1126/science.1228309