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Histone H2A cooperates with RIP2 to induce the expression of antibacterial genes and MHC related genes
Xiao Man Wu1, Lu Cao1, Pin Nie2
1State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, China; University of Chinese Academy of Sciences, Beijing, China.
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.
Insights
Zebrafish histone H2A exhibits antibacterial properties against Edwardsiella piscicida. Its expression and function are linked to RIP2, enhancing the immune response by upregulating antibacterial and MHC genes.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Histones, components of nucleosomes, can yield antimicrobial peptides (AMPs).
- While histone H2A-derived AMPs are known, the antimicrobial role of complete histone H2A is less understood.
- Zebrafish histone H2A's function in innate immunity requires further investigation.
Purpose of the Study:
- To functionally characterize zebrafish histone H2A.
- To investigate its role in antibacterial immunity against Edwardsiella piscicida.
- To elucidate the involvement of RIP2 in zebrafish histone H2A-mediated immune responses.
Main Methods:
- Gene expression analysis in zebrafish embryos and larvae under different conditions (basal, infection, RIP2 deficiency).
- Overexpression of zebrafish histone H2A in zebrafish larvae during Edwardsiella piscicida infection.
- Quantitative analysis of bacterial load and survival rates.
- Transcriptional analysis of antibacterial and MHC-related genes.
Main Results:
- Zebrafish histone H2A expression is higher in embryos and inducible by bacterial infection.
- RIP2 deficiency reduces zebrafish histone H2A expression.
- Overexpression of zebrafish histone H2A inhibits Edwardsiella piscicida proliferation and enhances larval survival.
- Zebrafish histone H2A overexpression upregulates antibacterial and MHC genes in a RIP2-dependent manner.
Conclusions:
- Complete zebrafish histone H2A possesses in vivo antibacterial activity against Edwardsiella piscicida.
- Zebrafish histone H2A cooperates with the adaptor protein RIP2 to regulate the transcription of antibacterial and MHC genes.
- This study highlights a novel role for complete histone H2A in innate immunity, mediated by RIP2.
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