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. 2021 Aug 31;6(4):e0074721.
doi: 10.1128/mSystems.00747-21. Epub 2021 Aug 17.

Bacterial Epigenomics: Coming of Age

Affiliations

Bacterial Epigenomics: Coming of Age

Pedro H Oliveira. mSystems. .

Erratum in

Abstract

Epigenetic DNA methylation in bacteria has been traditionally studied in the context of antiparasitic defense and as part of the innate immune discrimination between self and nonself DNA. However, sequencing advances that allow genome-wide analysis of DNA methylation at the single-base resolution are nowadays expanding and have propelled a modern epigenomic revolution in our understanding of the extent, evolution, and physiological relevance of methylation. Indeed, as the number of mapped bacterial methylomes recently surpassed 4,000, increasing evidence supports roles for methylation in gene expression regulation, virulence, and host colonization, among others. In this paper, I summarize lessons taken from high-dimensional methylome data analyses and recent efforts that we and others are developing to leverage such findings into meaningful biological insights and overarching frameworks. Ultimately, I highlight anticipated research avenues and technological developments likely to unfold in the coming years.

Keywords: antimicrobial; epigenetics; holoepigenomics; metaepigenomics; methylation; single cell.

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Conflict of interest statement

Conflict of Interest Disclosures: P.H.O. has nothing to disclose.

Conflict of Interest Disclosures: P.H.O. has nothing to disclose.

Figures

FIG 1
FIG 1
Approaches to study bacterial methylomes from clonal isolates, microbiomes, and holobionts. (A) Although a large abundance of methylomes profiled to date belongs to genome (G) isolates, there is a growing interest in the analysis of microbiome (M) and holobiont (H) methylomes. (B) Recent progress in third-generation sequencing technologies (e.g., SMRT-seq and nanopore sequencing) has enabled direct genome-wide detection of methylated positions and target motifs. (C) Relevant functional information on the epigenome can be obtained by targeted mutagenesis of DNA MTases. A comprehensive global transcriptome and functional profiling by RNA-seq offers the opportunity to further dissect the range of differentially expressed genes in a methylation-free strain. For metaepigenomes, nonlinear dimensionality reduction algorithms such as the t-distributed stochastic neighbor embedding (t-SNE) are a possible option to visualize and interpret methylation features across multiple metagenomic contigs. A phylogenetic representation of methylation systems’ density across several metagenome-assembled genomes may also provide clues into the interplay between DNA methylation and factors unique to the environment of each community. In holoepigenomes, genome-wide analysis of CpG site methylation differences between multiple hosts (as shown in the Manhattan plots of P values) may provide insight into the network of host genes whose expression is being significantly modulated by the presence of certain symbionts.

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