Understanding prokaryotic adaptation through advanced DNA methylation detection techniques

DNA methylation, a versatile epigenetic modification in prokaryotes, is a crucial regulator of various biological activities, such as genome defence, gene expression, and DNA repair. The most common DNA methylation form in prokaryotes is N6-methyladenine, where a methyl group is added to the adenine. Orphan and restriction-modification system methylases constitute the main methylation systems in prokaryotes. Prokaryotes can adapt to environmental fluctuations through orphan methylase regulation and phase variation of restriction-modification systems, which generate diversified methylomes that modulate the expression of genes. Modern sequencing techniques, including single-molecule real-time sequencing and Nanopore sequencing, enable the characterization of several methylation patterns simultaneously and facilitate the study of prokaryotic epigenomics. This review introduces the prokaryotic DNA methylation systems and prokaryotic adaptation through DNA methylation. Finally, we summarize the current sequencing techniques capable of characterizing methylation forms applicable to prokaryotes and their future perspectives.