Occurrence, evolution, and functions of DNA phosphorothioate epigenetics in bacteria

Abstract

The chemical diversity of physiological DNA modifications has expanded with the identification of phosphorothioate (PT) modification in which the nonbridging oxygen in the sugar-phosphate backbone of DNA is replaced by sulfur. Together with DndFGH as cognate restriction enzymes, DNA PT modification, which is catalyzed by the DndABCDE proteins, functions as a bacterial restriction-modification (R-M) system that protects cells against invading foreign DNA. However, the occurrence of systems across a large number of bacterial genomes and their functions other than R-M are poorly understood. Here, a genomic survey revealed the prevalence of bacterial systems: 1,349 bacterial systems were observed to occur sporadically across diverse phylogenetic groups, and nearly half of these occur in the form of a solitary gene cluster that lacks the restriction counterparts. A phylogenetic analysis of 734 complete PT R-M pairs revealed the coevolution of M and R components, despite the observation that several PT R-M pairs appeared to be assembled from M and R parts acquired from distantly related organisms. Concurrent epigenomic analysis, transcriptome analysis, and metabolome characterization showed that a solitary PT modification contributed to the overall cellular redox state, the loss of which perturbed the cellular redox balance and induced to reconfigure its metabolism to fend off oxidative stress. An in vitro transcriptional assay revealed altered transcriptional efficiency in the presence of PT DNA modification, implicating its function in epigenetic regulation. These data suggest the versatility of PT in addition to its involvement in R-M protection.

Characterization of a thaumarchaeal symbiont that drives incomplete nitrification in the tropical spongeIanthella basta

“…Nitrosopumilus salaria also encode this DNA modification system. These genes possibly encode a primitive immune system by enabling discrimination between self and non-self DNA (but can also epigenetically affect the transcriptome of bacteria; Tong et al 2018) and might thusin concert with the better understood canonical RM systems (Fig. S6)be particularly useful for sponge symbionts living in a system where they are prone to genetic exchanges.…”

Recent Advances in the Genomic Profiling of Bacterial Epigenetic Modifications

“…Unlike methylation‐based R‐M systems, DNA PT modification is only partial at a given site in a population of cells, even at the presence of the active restriction cognate DndFGH, indicating alternative roles of PT . Later studies by Tong et al demonstrated that PT modification is a versatile player in DNA epigenetic control and the maintenance of cellular redox homeostasis in Pseudomonas fluorescens . Taken together, these applications demonstrate that SMRT sequencing offers a powerful approach for exploring pervasive and diverse epigenetic markers, to determine the targets of methyltransferases or other modifying enzymes and provide insight into the effects of such modifications on biological processes.…”

“…Distinct from the methylation of nucleobases, DNA phosphorothioate (PT) modification is a newly identified type of epigenetic modification in which the non‐bridging oxygen in the sugar‐phosphate backbone is substituted with sulfur in a sequence‐selective and R P stereo‐specific manner . In addition to being a component of restriction‐modification (R‐M) systems, Tong et al reported that PT modification is involved in the epigenetic regulation of gene expression and maintenance of cellular redox homeostasis.…”

Gut microbiome interventions in human health and diseases

“…For instance, Leonard et al reported that different donor‐derived strains of the same species have inconsistent Dam methylation patterns, which might be a potential indicator for disease statues. Furthermore, considering the important physiological function of DNA phosphorothioation (PT) modification, analysis of PT modification of the intestinal microbiome may also deepen the understanding of its diversity. Diet and other environmental factors may alter the microbial environment in the host, but because of the functional redundancy across taxonomy, differences in compositional structure, especially at higher taxonomic levels, do not indicate altered microbiota‐host interactions.…”