Histone H2A cooperates with RIP2 to induce the expression of antibacterial genes and MHC related genes

Abstract An octamer consisting of two copies of histones H2A, H2B, H3 and H4 is the nucleosome core. It is well established that histone derived antimicrobial peptides (AMPs) have anti-microbial properties in various invertebrate and vertebrate species. Different from well-known histone H2A-derived AMPs, the antimicrobial properties of the complete histone H2A are rather limited. In the present study, we report the functional characterization of the complete histone H2A from zebrafish. The expression of zebrafish histone H2A was higher in embryos than in larvae, and inducible in response to bacterial infection. Furthermore, the expression of zebrafish histone H2A was decreased by RIP2 deficiency with and/or without bacterial infection. During Edwardsiella piscicida infection, the overexpression of zebrafish histone H2A inhibited bacterial proliferation and increased the survival rate of zebrafish larvae. The overexpression of zebrafish histone H2A demonstrated an increased transcription of many antibacterial genes and MHC related genes, which was dependent on RIP2, an adaptor protein for signal propagation of the NLRs-mediated antibacterial immune response. In line with this, zebrafish histone H2A cooperated with RIP2 to induce the transcription of many antibacterial genes and MHC related genes. All together, these results firstly demonstrate the antibacterial property of the complete histone H2A against gram-negative bacteria E. piscicida in vivo and the correlation between zebrafish histone H2A and RIP2 adaptor protein on the transcriptional regulation of antibacterial genes and MHC related genes.