Highlights
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DNA methylation is the epigenetic mark most commonly found throughout the living world. In bacteria, it is responsible for a variety of functional roles, including defense against foreign DNA, regulation of chromosome replication and segregation, mismatch repair, and control of virulence gene expression, among others.
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DNA methyltransferases (MTases) are responsible for transferring a methyl group from an S-adenosyl-l-methionine (AdoMet) donor to DNA. Dam, Dcm, and CcrM are examples of bacterial DNA MTases that have been comprehensively characterized for their roles in gene regulation.
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Here, we summarized the landscape of DNA MTase conservation in bacteria and observed that MTase conservation is more common than previously portrayed, spanning several phylogenetic levels, and being present in multiple human and animal pathogens. Information on the functional relevance of these MTases is virtually inexistent, but they are expected to play key functional roles.
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We also discuss why and how these MTases can be prioritized to enable a community-wide, integrative approach for functional epigenomic studies. Ultimately, we discuss how some highly conserved DNA MTases may emerge as promising targets for the development of novel epigenetic inhibitors for biomedical applications.
An increasing number of studies have reported that bacterial DNA methylation has important functions beyond the roles in restriction-modification systems, including the ability of affecting clinically relevant phenotypes such as virulence, host colonization, sporulation, biofilm formation, among others. Although insightful, such studies have a largely ad hoc nature and would benefit from a systematic strategy enabling a joint functional characterization of bacterial methylomes by the microbiology community. In this opinion article, we propose that highly conserved DNA methyltransferases (MTases) represent a unique opportunity for bacterial epigenomic studies. These MTases are rather common in bacteria, span various taxonomic scales, and are present in multiple human pathogens. Apart from well-characterized core DNA MTases, like those from Vibrio cholerae, Salmonella enterica, Clostridioides difficile, or Streptococcus pyogenes, multiple highly conserved DNA MTases are also found in numerous human pathogens, including those belonging to the genera Burkholderia and Acinetobacter. We discuss why and how these MTases can be prioritized to enable a community-wide, integrative approach for functional epigenomic studies. Ultimately, we discuss how some highly conserved DNA MTases may emerge as promising targets for the development of novel epigenetic inhibitors for biomedical applications.
Keywords
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Glossary
DNA methyltransferase
family of enzymes that catalyze the transfer of a methyl group from an S-adenosyl-l-methionine (AdoMet) donor to DNA.
Epigenome
complete record of all chemical modifications to DNA. Together with the epitranscriptome (chemical modifications of RNA) and epiproteome (chemical modifications of proteins), makes up the epi-ome.
Methylome
complete record of all methyl modifications to either DNA, RNA, or proteins in a particular cell or organism.
Restriction-modification (R-M) systems
almost ubiquitous in prokaryotes, these systems consist of a DNA methyltransferase that methylates a specific target sequence in the host genome and a cognate restriction endonuclease that cleaves unmethylated or inappropriately methylated targets from exogenous DNA. They are thus typically regarded as innate defense systems and, depending on type, as molecular parasites.
Single molecule real-time (SMRT) sequencing
third generation long-read sequencing-by-synthesis technology, based on the real-time imaging of fluorescently tagged nucleotides as they are synthesized along individual DNA template molecules. The duration between consecutive pulses of light directly reflects the DNA polymerase kinetics, including the impact caused by DNA modification events.
Article info
Publication history
Published online: May 13, 2020
Accepted: April 10, 2020
Received in revised form: March 19, 2020
Received: January 2, 2020
Identification
Copyright
© 2020 Elsevier Ltd. All rights reserved.
