Bacterial DNA Methylation and Methylomes

Formation of C5-methylcytosine, N4-methylcytosine, and N6-methyladenine in bacterial genomes is postreplicative and involves transfer of a methyl group from S-adenosyl-methionine to a base embedded in a specific DNA sequence context. Most bacterial DNA methyltransferases belong to restriction-modification systems; in addition, “solitary” or “orphan” DNA methyltransferases are frequently found in the genomes of bacteria and phage. Base methylation can affect the interaction of DNA-binding proteins with their cognate sites, either by a direct effect (e.g., steric hindrance) or by changes in DNA topology. In both Alphaproteobacteria and Gammaproteobacteria, the roles of DNA base methylation are especially well known for N6-methyladenine, including control of chromosome replication, nucleoid segregation, postreplicative correction of DNA mismatches, cell cycle-coupled transcription, formation of bacterial cell lineages, and regulation of bacterial virulence. Technical procedures that permit genome-wide analysis of DNA methylation are nowadays expanding our knowledge of the extent, evolution, and physiological significance of bacterial DNA methylation.