Histone deacetylase 3 contributes to the anti-viral innate immunity of macrophages through interacting with FOXK1 to regulate STAT1/2 transcription [RNA-seq]

It is well known that IFNa/ß activates the JAK/STAT signaling pathway and suppresses viral replication through induction of interferon stimulated genes (ISGs). Here we reported that knockout of HDAC3 from macrophages resulted in decreased expression of STAT1 and STAT2, leading to a defective anti-viral immunity in cells and mice. Further studies showed that HDAC3 interacted with a conserved transcription factor Forkhead Box K1 (FOXK1), co-localized with FOXK1 at the promoter of STAT1 and STAT2, and was required for protecting FOXK1 from lysosomal system mediated degradation. Constantly, FOXK1 deficient macrophages also showed low STAT1 and STAT2 expression with defective response to virus. Thus, our studies uncovered the biological importance of HDAC3 on regulating antiviral immunity of macrophages through interaction with FOXK1 to regulate the expression of STAT1 and STAT2. Overall design: Total RNA profiling of gene expression upon knock-out of Hdac3 or Foxk1 in RAW264.7 cells after stimulated with vesicular stomatitis virus for 8h