Keiko Ozato heads the Section on Molecular Genetics of Immunity. The Section studies gene regulation in innate immunity, focusing on the role of chromatin. The group showed that the transcription factor IRF8 plays a central role in eliciting innate anti-pathogen resistance in macrophages and dendritic cells. The group's recent analyses show that pathogen stimulation alters SUMO modification of numerous nuclear proteins leading to a global shift in gene expression patterns in macrophages. The study also found that SUMO modification is an important mechanism by which to control IRF8 transcriptional activity. The group previously showed that the bromodomain protein BRD4 binds to acetylated chromatin and the elongation factor P-TEFb to stimulate transcription. Studying interferon (IFN) stimulation as a model for innate immunity, the Section showed that IFN triggers the recruitment of BRD4 to IFN–stimulated genes and that this recruitment is the primary event that initiates productive elongation. The Section's subsequent work with this model revealed that transcription leads to a large-scale exchange of chromatin in the IFN–stimulated genes, replacing the standard histone H3 with the variant H3.3. The exchange led to the formation of a lasting mark signifying earlier transcription of IFN–stimulated genes.
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