The laboratory headed by Keiko Ozato  is interested in chromatin and gene regulation in innate immunity. We study the role of three nuclear factors, histone H3.3, BRD4, and IRF8. Histone H3.3 is a variant histone that is incorporated into nucleosomes during transcriptional elongation, a defining feature of this variant. Other canonical core histones are deposited into nucleosomes during replication. For this reason, H3.3 is thought to be involved in epigenetic memory created after transcription, although experimental evidence for memory formation/maintenance is scant. BRD4 is a bromodomain protein of the BET family, expressed broadly in many cells, from early embryos to adults. Through the bromodomain, BRD4 binds to acetylated but not unacetylated histones. BRD4 is thus called a “chromatin reader,” a type of regulatory factor capable of conveying epigenome information to gene expression. Furthermore, BRD4 binds to the elongation factor complex P-TEFb through the C-terminal domain, and drives transcription of many genes by driving RNA polymerase II to move through the gene body, generating nascent mRNA. Many recent reports point out that BRD4 promotes growth of cancer cells, including various blood cancers, by mediating the formation of super-enhancers involved in cell-cycle progression. IRF8  is a DNA–binding transcription factor that plays an essential role in innate resistance against a wide array of pathogens (Figure 1A for its structure). We discovered IRF8 in 1990. IRF8 is expressed mostly in cells of the myeloid lineage, including monocytes/macrophages, dendritic cells, and microglia. IRF8 is strongly induced when stimulated by interferons (IFN). In addition, it is upregulated when myeloid cells encounter pathogen-derived molecules and agents produced by stress. In turn, IRF8 activates many genes important for host resistance. IRF8–induced genes include those involved in autophagy and lysosome-mediated pathogen clearance; IRF8 does so by binding to small DNA motifs present in promoter and enhancer regions of the target genes.