Epigenetic Gene Regulation in the Bacterial World

Abstract

SUMMARY Like many eukaryotes, bacteria make widespread use of postreplicative DNA methylation for the epigenetic control of DNA-protein interactions. Unlike eukaryotes, however, bacteria use DNA adenine methylation (rather than DNA cytosine methylation) as an epigenetic signal. DNA adenine methylation plays roles in the virulence of diverse pathogens of humans and livestock animals, including pathogenic Escherichia coli, Salmonella, Vibrio, Yersinia, Haemophilus, and Brucella. In Alphaproteobacteria, methylation of adenine at GANTC sites by the CcrM methylase regulates the cell cycle and couples gene transcription to DNA replication. In Gammaproteobacteria, adenine methylation at GATC sites by the Dam methylase provides signals for DNA replication, chromosome segregation, mismatch repair, packaging of bacteriophage genomes, transposase activity, and regulation of gene expression. Transcriptional repression by Dam methylation appears to be more common than transcriptional activation. Certain promoters are active only during the hemimethylation interval that follows DNA replication; repression is restored when the newly synthesized DNA strand is methylated. In the E. coli genome, however, methylation of specific GATC sites can be blocked by cognate DNA binding proteins. Blockage of GATC methylation beyond cell division permits transmission of DNA methylation patterns to daughter cells and can give rise to distinct epigenetic states, each propagated by a positive feedback loop. Switching between alternative DNA methylation patterns can split clonal bacterial populations into epigenetic lineages in a manner reminiscent of eukaryotic cell differentiation. Inheritance of self-propagating DNA methylation patterns governs phase variation in the E. coli pap operon, the agn43 gene, and other loci encoding virulence-related cell surface functions.

Convergence of DNA methylation and phosphorothioation epigenetics in bacterial genomes

“…Despite the absence of cognate REases, orphan MTases still confer immunity against the virulence of a parasitic R-M complex with the same target sites (9). In addition to defense against bacteriophages and transposons, DNA methylation is involved in various cellular functions, including chromosome replication, DNA mismatch repair, transcriptional regulation, transposition, and pathogenesis (1,10,11).…”

“…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).…”

Gene silencing is an ancient means of producing multiple phenotypes from the same genotype

“…Bacteria use DNA methylation (of adenine and of cytosine) both as a primitive immune system through restrictionmodification and to provide signals for DNA replication, mismatch repair and transcription [3]. For example, DNA methylation controls the heritable expression of Pyelonephritis-associated pili (Pap) [4].…”

“…Pap are hair-like appendages that play a role in attachment of bacteria to cells lining the mammalian urinary tract, facilitating colonisation of the kidneys. Expression of the genes controlling pili production is either ON or OFF in any individual cell of the population [3]. The switch rate is low (and, as far as we know, stochastic) so most, but not all, daughter cells acquire the same state as the parent cell.…”

Escherichia coli DNA Adenine Methyltransferase

“…Unlike most bacterial methyltransferases, EcoDam does not belong to a restriction-modification system that serves to protect the cell from foreign DNA. Instead, the methylation by EcoDam of the ϳ20,000 GATC sites within the E. coli genome is critical in a number of biological pathways including gene regulation, chromosome replication, mismatch repair, and nucleoid structure determination (11,12). It has been shown that there are relatively few EcoDam molecules per bacterial cell suggesting that high processivity is essential in the methylation of the large number of GATC sites in the E. coli genome to avoid hyper-mutating phenotypes (10,11,13).…”