Bacterial Epigenomics: Epigenetics in the Age of Population Genomics

Abstract

Genome methylation in bacteria is an area of intense interest because it has broad implications for bacteriophage resistance, replication, genomic diversity via replication fidelity, response to stress, gene expression regulation, and virulence. Increasing interest in bacterial DNA modification is coming about with investigation of host/microbe interactions and the microbiome association and coevolution with the host organism. Since the recognition of DNA methylation being important in Escherichia coli and bacteriophage resistance using restriction/modification systems, more than 43,600 restriction enzymes have been cataloged in more than 3600 different bacteria. While DNA sequencing methods have made great advances there is a dearth of method advances to examine these modifications in situ. However, the large increase in whole genome sequences has led to advances in defining the modification status of single genomes as well as mining new restriction enzymes, methyltransferases, and modification motifs. These advances provide the basis for the study of pan-epigenomes, population-scale comparisons among pangenomes to link replication fidelity and methylation status along with mutational analysis of mutLS. Newer DNA sequencing methods that include SMRT and nanopore sequencing will aid the detection of DNA modifications on the ever-increasing whole genome and metagenome sequences that are being produced. As more sequences become available, larger analyses are being done to provide insight into the role and guidance of bacterial DNA modification to bacterial survival and physiology.

Impacts of Mycoplasma agalactiae restriction-modification systems on pan-epigenome dynamics and genome plasticity

“…While this highlights the importance of MTases and RM systems in mycoplasmas, their role in cellular regulation and HGT has yet to be addressed. Genome methylation in bacteria is an area of great interest because of its broad implications for evolution, biology, and virulence [ 27 ]. The development of real-time single molecule sequencing (SMRT-seq) has allowed the detection of methylated bases, whether on a plasmid or bacterial chromosome, and is particularly suited to small mycoplasma genomes.…”

Extension of bacterial rDNA sequencing to concurrent epigenetic analysis and its application to 16S meta-epigenetics

“…The copyright holder for this preprint this version posted February 16, 2022. ; https://doi.org/10.1101/2022.02. 15.480630 doi: bioRxiv preprint in this combination analysis, including a degenerated universal primer (Figure 1) targeting the 16S rDNA region that detects 0% to 100% methylcytosine content at the primer site. This universal primer set can target both bisulfite-treated and non-bisulfite-treated bacterial genomic DNA (Figure 1), therefore bisulfite PCR and sequencing can provide information on the methylation status of the 16S rDNA sequence in parallel with the targeted 16S rDNA sequence itself.…”

“…However, this new meta-epigenomic technique is based on sequencing the whole genome and/or all nucleic acids in a sample. Thus, it loses the advantages of 16S rDNA analysis, which analyzes a narrow region of bacterial DNA but can identify a wide range of bacterial genera or species even from small-volume samples (15).…”

MeStudio: crossing methylation and genomic features for comparative epigenomic analyses

“…Phenotypic plasticity, stress responses and acclimation display significant contribution from epigenetic mechanisms (Moler et al , 2019). Among epigenetic modifications, DNA methylation has been shown to be key in the control of several biological phenomena in eukaryotes and prokaryotes (Jones, 2012) and in the last years the study of variation in epigenetic response is stirring the attention of several investigators (Chen et al , 2020). Third-generation sequencing technologies, namely single molecule real-time (SMRT) (Flusberg et al , 2010;Fang et al , 2012) and nanopore ONT (Clarke et al , 2009;Simpson et al , 2017) sequencing allow to directly identify the most commonly methylated bases (Gouil and Keniry, 2019;Sánchez-Romero and Casadesús, 2020;Rand et al , 2017).…”