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.