The Epigenomic Landscape of Prokaryotes

Abstract

DNA methylation acts in concert with restriction enzymes to protect the integrity of prokaryotic genomes. Studies in a limited number of organisms suggest that methylation also contributes to prokaryotic genome regulation, but the prevalence and properties of such non-restriction-associated methylation systems remain poorly understood. Here, we used single molecule, real-time sequencing to map DNA modifications including m6A, m4C, and m5C across the genomes of 230 diverse bacterial and archaeal species. We observed DNA methylation in nearly all (93%) organisms examined, and identified a total of 834 distinct reproducibly methylated motifs. This data enabled annotation of the DNA binding specificities of 620 DNA Methyltransferases (MTases), doubling known specificities for previously hard to study Type I, IIG and III MTases, and revealing their extraordinary diversity. Strikingly, 48% of organisms harbor active Type II MTases with no apparent cognate restriction enzyme. These active ‘orphan’ MTases are present in diverse bacterial and archaeal phyla and show motif specificities and methylation patterns consistent with functions in gene regulation and DNA replication. Our results reveal the pervasive presence of DNA methylation throughout the prokaryotic kingdoms, as well as the diversity of sequence specificities and potential functions of DNA methylation systems.

Convergence of DNA methylation and phosphorothioation epigenetics in bacterial genomes

“…In particular, methylation-based R-M systems and epigenetic marks have been detected in the vast majority of bacterial and archaeal genomes (3,30). The chemical diversity of DNA modifications in bacteria has recently grown beyond methylation with the discovery of 7-deazaguanine modifications (2) and PT modifications of the DNA backbone (12,15).…”

“…DNA phosphorothioation | DNA methylation | epigenetics | restriction-modification | bioanalytical chemistry T he emergence of convergent technologies has led to a growing appreciation for the diversity of DNA modifications in microbial epigenetics and restriction-modification (R-M) systems (1)(2)(3). DNA methylation, the most extensively studied genetic modification, was originally discovered in bacteria in the context of R-M systems involving a methyltransferase (MTase) that modifies "self" DNA at specific target sites and a cognate restriction endonuclease (REase) that discriminates and destroys unmodified invading DNA (3)(4)(5).…”

“…DNA methylation, the most extensively studied genetic modification, was originally discovered in bacteria in the context of R-M systems involving a methyltransferase (MTase) that modifies "self" DNA at specific target sites and a cognate restriction endonuclease (REase) that discriminates and destroys unmodified invading DNA (3)(4)(5). R-M systems are ubiquitous in prokaryotes and are classified into four types (I, II, III, and IV) based on their molecular structure, sequence recognition, cleavage position, and cofactor requirements (3,6,7). However, some MTases exist alone, without an apparent cognate REase partner.…”

Widespread adenine N6-methylation of active genes in fungi

“…While 5-methylcytosine (5mC) has been well-established as an epigenomic mark in eukaryotes 6 , 6mA has been predominantly appreciated as a modification of prokaryotic genomes 7 and eukaryotic RNA 8 . However, genomic 6mA has recently been demonstrated to play crucial roles in both gene and transposon regulation, where it either (i) suppresses expression of transposable elements in animals during development [2][3][4] or (ii) is associated with promoters of actively expressed genes and is involved in nucleosome positioning in algae 1 .…”

A DNS-metiláció szerepe és megváltozása az öregedés és a daganatos betegségek kialakulása során

“…A DNS-metiláció a prokarióták, az eukarióták és a ví-rusok körében is megfigyelhető epigenetikai módosulás [3,4], amely 6-metiladenin, 4-metilcitozin és 5-metilcitozin formájában fordul elő leggyakrabban [3]. A fenti ÖSSZEFOGLALÓ KÖZLEMÉNY posztreplikatív módon létrejövő metilált bázismódosula-tok metiltranszferáz enzimek által katalizált kovalens módosítások [3,4].…”