Molecular Identification of Two DNA Methyltransferase Genes and Their Functional Characterization in the Anti-Bacterial Immunity of

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Jun 2

PMID 35651618

Authors

Saima Kausar

Muhammad Nadeem Abbas

Isma Gul

Ruochen Liu

Qianqian Li

Erhu Zhao

Muhan Lv

Hongjuan Cui

Affiliations

Soon will be listed here.

Abstract

Under different physiological conditions, such as microbial infection, epigenetic mechanisms regulate genes at the transcription level in living organisms. DNA methylation is a type of epigenetic mechanism in which DNA methyltransferases modify the expression of target genes. Here, we identified a full-length sequence of DNMT-1 and DNMT-2 from the Chinese oak silkworm, , which was highly similar to the homologous sequences of . ApDNMT-1 and ApDNMT-2 have unique domain architectures of insect DNMTs, highlighting their conserved functions in . and were found to be widely expressed in various tissues, with the highest levels of expression in hemocytes, the ovary, testis, and fat bodies. To understand the biological role of these genes in microbial resistance, we challenged the fifth instar larvae of by administrating Gram-positive and Gram-negative bacteria and fungi. The results revealed that transcript levels of and were increased compared to the control group. The inhibition of these genes by a DNMTs inhibitor [5-azacytidine (5-AZA)] significantly reduced bacterial replication and larvae mortality. In addition, 5-AZA treatment modified the expression patterns of antimicrobial peptides (AMPs) in the larvae. Our results suggest that and seem to have a crucial role in innate immunity, mediating antimicrobial peptide responses against bacterial infection in .

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References

Biergans S, Galizia C, Reinhard J, Claudianos C . Dnmts and Tet target memory-associated genes after appetitive olfactory training in honey bees. Sci Rep. 2015; 5:16223. PMC: 4632027. DOI: 10.1038/srep16223. View

Lim K, Park E, Kim D, Cho K, Kim K, Park Y . Suppression of interferon-mediated anti-HBV response by single CpG methylation in the 5'-UTR of . Gut. 2017; 67(1):166-178. DOI: 10.1136/gutjnl-2016-312742. View

Zhang G, Hussain M, ONeill S, Asgari S . Wolbachia uses a host microRNA to regulate transcripts of a methyltransferase, contributing to dengue virus inhibition in Aedes aegypti. Proc Natl Acad Sci U S A. 2013; 110(25):10276-81. PMC: 3690878. DOI: 10.1073/pnas.1303603110. View

Kweh M, Merriman K, Nelson C . Short communication: Inhibition of DNA methyltransferase and histone deacetylase increases β-defensin expression but not the effects of lipopolysaccharide or 1,25-dihydroxyvitamin D in bovine mammary epithelial cells. J Dairy Sci. 2019; 102(6):5706-5712. DOI: 10.3168/jds.2018-16141. View

Capuano F, Mulleder M, Kok R, Blom H, Ralser M . Cytosine DNA methylation is found in Drosophila melanogaster but absent in Saccharomyces cerevisiae, Schizosaccharomyces pombe, and other yeast species. Anal Chem. 2014; 86(8):3697-702. PMC: 4006885. DOI: 10.1021/ac500447w. View

Kausar S, Abbas M, Qian C, Zhu B, Gao J, Sun Y . Role of Antheraea pernyi serpin 12 in prophenoloxidase activation and immune responses. Arch Insect Biochem Physiol. 2017; 97(2). DOI: 10.1002/arch.21435. View

Abbas M, Kausar S, Gul I, Ke X, Dong Z, Lu X . Suppressor of cytokine signalling 6 is a potential regulator of antimicrobial peptides in the Chinese oak silkworm, Antheraea pernyi. Mol Immunol. 2021; 140:12-21. DOI: 10.1016/j.molimm.2021.10.001. View

Okamoto Y, Shinjo K, Shimizu Y, Sano T, Yamao K, Gao W . Hepatitis virus infection affects DNA methylation in mice with humanized livers. Gastroenterology. 2013; 146(2):562-72. DOI: 10.1053/j.gastro.2013.10.056. View

Baradaran E, Moharramipour S, Asgari S, Mehrabadi M . Induction of DNA methyltransferase genes in Helicoverpa armigera following injection of pathogenic bacteria modulates expression of antimicrobial peptides and affects bacterial proliferation. J Insect Physiol. 2019; 118:103939. DOI: 10.1016/j.jinsphys.2019.103939. View

10.

Xu G, Zhang J, Lyu H, Song Q, Feng Q, Xiang H . DNA methylation mediates BmDeaf1-regulated tissue- and stage-specific expression of BmCHSA-2b in the silkworm, Bombyx mori. Epigenetics Chromatin. 2018; 11(1):32. PMC: 6001065. DOI: 10.1186/s13072-018-0202-4. View

11.

Gegner J, Baudach A, Mukherjee K, Halitschke R, Vogel H, Vilcinskas A . Epigenetic Mechanisms Are Involved in Sex-Specific -Generational Immune Priming in the Lepidopteran Model Host . Front Physiol. 2019; 10:137. PMC: 6410660. DOI: 10.3389/fphys.2019.00137. View

12.

Li E . Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet. 2002; 3(9):662-73. DOI: 10.1038/nrg887. View

13.

Looney M, Lorenc R, Halushka M, Karakousis P . Key Macrophage Responses to Infection With Are Co-Regulated by microRNAs and DNA Methylation. Front Immunol. 2021; 12:685237. PMC: 8204050. DOI: 10.3389/fimmu.2021.685237. View

14.

Pacis A, Tailleux L, Morin A, Lambourne J, MacIsaac J, Yotova V . Bacterial infection remodels the DNA methylation landscape of human dendritic cells. Genome Res. 2015; 25(12):1801-11. PMC: 4665002. DOI: 10.1101/gr.192005.115. View

15.

Lyko F, Maleszka R . Insects as innovative models for functional studies of DNA methylation. Trends Genet. 2011; 27(4):127-31. DOI: 10.1016/j.tig.2011.01.003. View

16.

Standage D, Berens A, Glastad K, Severin A, Brendel V, Toth A . Genome, transcriptome and methylome sequencing of a primitively eusocial wasp reveal a greatly reduced DNA methylation system in a social insect. Mol Ecol. 2016; 25(8):1769-84. DOI: 10.1111/mec.13578. View

17.

Abbas M, Zhu B, Kausar S, Dai L, Sun Y, Tian J . Suppressor of cytokine signaling 2-12 regulates antimicrobial peptides and ecdysteroid signaling pathways in Bombyx mori (Dazao). J Insect Physiol. 2017; 103:47-56. DOI: 10.1016/j.jinsphys.2017.10.004. View

18.

Goto A, Fukuyama H, Imler J, Hoffmann J . The chromatin regulator DMAP1 modulates activity of the nuclear factor B (NF-B) transcription factor Relish in the Drosophila innate immune response. J Biol Chem. 2014; 289(30):20470-6. PMC: 4110259. DOI: 10.1074/jbc.C114.553719. View

19.

Xiang H, Zhu J, Chen Q, Dai F, Li X, Li M . Single base-resolution methylome of the silkworm reveals a sparse epigenomic map. Nat Biotechnol. 2010; 28(5):516-20. DOI: 10.1038/nbt.1626. View

20.

Niwa T, Toyoda T, Tsukamoto T, Mori A, Tatematsu M, Ushijima T . Prevention of Helicobacter pylori-induced gastric cancers in gerbils by a DNA demethylating agent. Cancer Prev Res (Phila). 2013; 6(4):263-70. DOI: 10.1158/1940-6207.CAPR-12-0369. View