IFI16: At the interphase between innate DNA sensing and genome regulation

DNA carries the genetic code, and is also a potent stimulator of innate immune responses. IFI16 is a member of the family of PYHIN proteins and is composed of a PYRIN domain involved in homotypic protein-protein interactions and two HIN domains mediating DNA binding. PYHIN proteins have been described to possess functions as innate pattern recognition receptors or transcriptional regulators. Interestingly, it is now emerging that IFI16, which exhibits both nuclear and cytosolic location, possesses both of these functions. In this review we discuss the current literature on IFI16 and propose key questions now facing this field of research. We propose that IFI16 plays a central role in the close interaction between the innate immune system and cellular regulation of the genome.