Introductions:Studies are still required to elucidate detailed regulator mechanisms initiated by PRRs in antiviral innate response.KAT8 is a histone acetyl transferase (HAT) that specifically acetylates lysine 16 of histone H4 (H4K16ac), the role of KAT8 in innate immunity has not been reported.
Methods: Q-PCR analysis of IFN-β，IFN-α mRNA in KAT8 knockdown macrophages; Luciferase activity of an IFN-β reporter in HEK293T cells transfected with control vector(Mock)or vector encoding KAT8,assessed by dual-luciferase assay;Immunoblot analysis of the interaction of KAT8 and IRF3 in HEK293T cells transfected to overexpress His-tagged KAT8 plasmid or mutant KAT8 plasmids; ChIP analysis of IRF3 recruitment to Ifnb/a promoter regions.
Results: Silencing of KAT8 selectively promotes Virus-induced production of type I interferon in macrophages; .KAT8 inhibits IFN-β luciferase activity by targeting IRF3;KAT8 interacts with IRF3 through its MYST domain;KAT8 enhances IRF3 acetylation through its MYST domain; Silencing of KAT8 promotes the recruitment of IRF3 to Ifnb/a promoter regions.
Conclusions: Upon infection with RNA or DNA viruses, host cells can induce the production of type I interferon. When KAT8 is involved, it can enhance IRF3 acetylation and inhibit the recruitment of IRF3 to Ifn b/a promoter regions, decreasing the production of type I interferon.