Keiko Ozato and colleagues in the Section on Molecular Genetics of Immunity study the molecular mechanisms underlying innate immunity endowed by macrophages and dendritic cells. The main aim of the group are [a] to elucidate how MF/DC regulate transcription in response to pathogens and inflammatory signals and [b] clarify the role of chromatin in the process. Their recent study on IRF8, a transcription factor they have isolated years ago and essential for the function of MF/DC macrophages and dendritic cells revealed that this factor is modified by phosphorylation, ubiquitination and sumoylation in a signal dependent manner, which profoundly affects the ability of IRF8 to regulate target gene transcription. Their study on the chromatin binding protein, Brd4 is making an interesting advancement through the use of a small molecule inhibitor made available through collaboration. Their analysis indicates that Brd4 is recruited to the interferon stimulated genes to direct the subsequent transcriptional elongation processes. This group has extended their research on the histone variant, H3.3 and reported that H3.3 is deposited in the interferon stimulated genes upon stimulation. The induced H3.3 incorporation displayed a novel pattern of deposition, later found to be linked to methylation of a specific lysine residue.
