DNA methylation plays critical roles in gene regulation in bacteria, from regulating essential processes like the cell cycle to phenotypes of practical interest like pathogenicity and motility. Synthetic manipulation of global methylation levels has broad impacts on cellular physiology, changing expression patterns of hundreds of genes. However, whether or how environmental variation in natural settings similarly impacts DNA methylation patterns has been unclear. In this work, using the alphaproteobacteria Methylobacterium extorquens and Caulobacter crescentus as model systems, we discover the methylome is highly fluid in response to environmental variation, with different environments leading to distinct patterns of increased or decreased methylation levels along the chromosome. Despite a heterogeneous effect of different environments on methylation patterns, we find a general principle where the dependence of methylation states on position in the genome decreases in proportion to growth rate. A simple model that considers the methylation state through different phases of the cell cycle as a function of distance from an origin provides a framework to interpret the effects of different stressors upon the observed environmental responsiveness of the methylation patterns. Our work highlights how sequencing data alone can shed light on important aspects of microbial physiology.
Mall, A., Abbaspour, M. H., Mathes, D. J., Udekwu, K. I., Marx, C. J.
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