Genome-wide lone strand adenine methylation in Deinococcus radiodurans R1: Regulation of gene expression through DR0643-dependent adenine methylation

• Published in: Microbiological research 2022-04, Vol.257, p.126964-126964, Article 126964
• Main Authors: Joshi, Suraj, Ghosh, Payel, Barage, Sagar, Basu, Bhakti, Deobagkar, Deepti D.
• Format: Article
• Language: English
• Subjects: Adenine; Adenine methylome; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biofilm; D. radiodurans; Deinococcus - genetics; Deinococcus - metabolism; DNA Methylation; DNA Repair; Gene regulation; Molecular Docking Simulation; Protein Processing, Post-Translational; SMRT sequencing; Transcriptome
• ISSN: 0944-5013; 1618-0623
• DOI: 10.1016/j.micres.2022.126964

•It is the first report of genome-wide adenine methylation and it's correlation with gene expression in D. radiodurans.•Findings confirm major contribution and epigenetic modulation by Dam1DR protein, followed by Dam2DR in D. radiodurans.•Adenine methylation contributed by Dam1DR controls various metabolic, transport pathways as well as signal transduction.•The present findings also highlighted the molecular interactions of Dam1DR with DNA and SAM by molecular modelling study. DNA methylation is a covalent modification of adenine or cytosine in the genome of an organism and is found in diverse microbes including the radiation resistant bacterium Deinococcus radiodurans R1. Although earlier findings have confirmed repression or de-repression of certain genes in adenine methyltransferase (DR_0643/Dam1DR) deficient D. radiodurans mutant however, the overall regulatory aspects of Dam1DR-mediated adenine methylation remain mostly unexplored. In the present study, we compared the genome-wide methylome and the corresponding transcriptome of D. radiodurans WT and Δdam1 mutant to explore the correlation between methylation and gene expression. In D. radiodurans, deletion of DR_0643 ORF (Δdam1) led to hypomethylation of 512 genes resulting in differential expression of 168 genes (99 genes are upregulated and 69 genes are downregulated). The modification patterns deduced for Dam1DR (DR_0643) and Dam2DR (DR_2267) were non-palindromic and atypical. Moreover, we observed methylation at opportunistic sites that show adenine methylation only in D. radiodurans Δdam1 and not in D. radiodurans WT. Correlation between the methylome and transcriptome suggests that hypomethylation at Dam1DR specific sites had both negative as well as a positive effects on gene expression. Pathways such as amino acid metabolism, transport, oxidative phosphorylation, quorum sensing, signal transduction, two-component system, glycolysis/gluconeogenesis, TCA cycle, glyoxylate and dicarboxylate metabolism were modulated by Dam1DR-mediated adenine methylation in D. radiodurans. Processes such as DNA repair, recombination, ATPase and transmembrane transporter activity were enriched when Dam1DR mutant was subjected to radiation stress. We further evaluated the molecular interactions and mode of binding between Dam1DR protein and S-adenosyl methionine using molecular docking followed by MD simulation. To get a better insight into the methylation mechanism, the Dam1DR-SAM complex was also docked with a D