Bacterial DNA Methylation and Methylomes

Abstract

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.

Prophages in Salmonella enterica: a driving force in reshaping the genome and physiology of their bacterial host?

“…One of the most studied DNA modifications is responsible for an epigenetic regulation called phase variation and occurs only in a small fraction of the bacterial population. This regulation relies on the methylation of deoxyadenosines by the Dam methylase (Deoxyadenosine methyltransferase) (Casadesús, ). The Dam enzyme recognizes and specifically modifies the 5′‐GATC‐3′ sequences; when these sequences are localized in a promoter region, methylation events can block the binding of transcriptional regulators and consequently modify gene expression.…”

The complete methylome of an entomopathogenic bacterium reveals the existence of loci with unmethylated Adenines

“…DNA methyltransferases (MTases) are enzymes that catalyze the transfer of a methyl group from the universal methyl donor S-Adenosylmethionine (SAM) to a nucleotide 1 . MTases are widespread from eukaryotes to prokaryotes: 5-methylcytosine (m5C) and N 6 -methyladenine (m6A) methylation marks have been described in eukaryotes 2 , 3 whereas additional N 4 -methylcytosine (m4C) marks can be detected in bacteria and archaea 4 , 5 . For years, DNA methylation studies mostly used whole genome bisulfite sequencing (WGBS), which only detects m5C 6 , until the advent of Single Molecule Real Time (SMRT) sequencing made it possible to also detect m4C and m6A modifications 7 .…”

“…During replication, errors may occur, and the MMR system excises the wrong base on the newly-synthesized unmethylated DNA strand 10 . The MMR system requires Dam ( D NA a denine M Tase), an MTase that is not coupled with a restriction enzyme and so called “orphan” or “solitary” MTase 5 . In Gammaproteobacteria , Dam methylates 5′-GATC-3′ motifs.…”

DNA Adenine Methyltransferase (Dam) Overexpression Impairs Photorhabdus luminescens Motility and Virulence

“…Numerous DNA methyltransferases (MTases) are a component of restriction-modification (RE) systems that protect the bacterial cell from invasion by bacteriophages DNA (Marinus and Løbner-Olesen, 2014 ). Other MTases are not linked to restriction endonuclease and are classified as “orphan” MTases (Casadesus, 2016 ). The best characterized orphan MTase in bacteria is Dam (DNA adenine methyltransferase), originally identified in Escherichia coli and widespread among gamma-proteobacteria (Lobner-Olesen et al, 2005 ).…”