Deciphering Bacterial Epigenomes Using Modern Sequencing Technologies

Overview

Journal Nat Rev Genet

Specialty Genetics

Date 2018 Dec 15

PMID 30546107

Citations 99

Authors

John Beaulaurier

Eric E Schadt

Gang Fang

Affiliations

Soon will be listed here.

Abstract

Prokaryotic DNA contains three types of methylation: N6-methyladenine, N4-methylcytosine and 5-methylcytosine. The lack of tools to analyse the frequency and distribution of methylated residues in bacterial genomes has prevented a full understanding of their functions. Now, advances in DNA sequencing technology, including single-molecule, real-time sequencing and nanopore-based sequencing, have provided new opportunities for systematic detection of all three forms of methylated DNA at a genome-wide scale and offer unprecedented opportunities for achieving a more complete understanding of bacterial epigenomes. Indeed, as the number of mapped bacterial methylomes approaches 2,000, increasing evidence supports roles for methylation in regulation of gene expression, virulence and pathogen-host interactions.

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References

Dalia A, Lazinski D, Camilli A . Characterization of undermethylated sites in Vibrio cholerae. J Bacteriol. 2013; 195(10):2389-99. PMC: 3650525. DOI: 10.1128/JB.02112-12. View

Dybvig K, Sitaraman R, French C . A family of phase-variable restriction enzymes with differing specificities generated by high-frequency gene rearrangements. Proc Natl Acad Sci U S A. 1998; 95(23):13923-8. PMC: 24968. DOI: 10.1073/pnas.95.23.13923. View

Kumar S, Cheng X, Klimasauskas S, Mi S, Posfai J, Roberts R . The DNA (cytosine-5) methyltransferases. Nucleic Acids Res. 1994; 22(1):1-10. PMC: 307737. DOI: 10.1093/nar/22.1.1. View

Seib K, Peak I, Jennings M . Phase variable restriction-modification systems in Moraxella catarrhalis. FEMS Immunol Med Microbiol. 2002; 32(2):159-65. DOI: 10.1111/j.1574-695X.2002.tb00548.x. View

Luo G, Wang F, Weng X, Chen K, Hao Z, Yu M . Characterization of eukaryotic DNA N(6)-methyladenine by a highly sensitive restriction enzyme-assisted sequencing. Nat Commun. 2016; 7:11301. PMC: 4835550. DOI: 10.1038/ncomms11301. View

Hsieh P . Molecular mechanisms of DNA mismatch repair. Mutat Res. 2001; 486(2):71-87. DOI: 10.1016/s0921-8777(01)00088-x. View

Leonard M, Davis-Richardson A, Ardissone A, Kemppainen K, Drew J, Ilonen J . The methylome of the gut microbiome: disparate Dam methylation patterns in intestinal Bacteroides dorei. Front Microbiol. 2014; 5:361. PMC: 4101878. DOI: 10.3389/fmicb.2014.00361. View

Baylin S, Jones P . A decade of exploring the cancer epigenome - biological and translational implications. Nat Rev Cancer. 2011; 11(10):726-34. PMC: 3307543. DOI: 10.1038/nrc3130. View

Balbontin R, Rowley G, Pucciarelli M, Lopez-Garrido J, Wormstone Y, Lucchini S . DNA adenine methylation regulates virulence gene expression in Salmonella enterica serovar Typhimurium. J Bacteriol. 2006; 188(23):8160-8. PMC: 1698197. DOI: 10.1128/JB.00847-06. View

10.

Tan A, Atack J, Jennings M, Seib K . The Capricious Nature of Bacterial Pathogens: Phasevarions and Vaccine Development. Front Immunol. 2016; 7:586. PMC: 5149525. DOI: 10.3389/fimmu.2016.00586. View

11.

Boye E, Stokke T, Kleckner N, Skarstad K . Coordinating DNA replication initiation with cell growth: differential roles for DnaA and SeqA proteins. Proc Natl Acad Sci U S A. 1996; 93(22):12206-11. PMC: 37968. DOI: 10.1073/pnas.93.22.12206. View

12.

Takahashi N, Naito Y, Handa N, Kobayashi I . A DNA methyltransferase can protect the genome from postdisturbance attack by a restriction-modification gene complex. J Bacteriol. 2002; 184(22):6100-8. PMC: 151934. DOI: 10.1128/JB.184.22.6100-6108.2002. View

13.

Davis B, Chao M, Waldor M . Entering the era of bacterial epigenomics with single molecule real time DNA sequencing. Curr Opin Microbiol. 2013; 16(2):192-8. PMC: 3646917. DOI: 10.1016/j.mib.2013.01.011. View

14.

Schadt E, Banerjee O, Fang G, Feng Z, Wong W, Zhang X . Modeling kinetic rate variation in third generation DNA sequencing data to detect putative modifications to DNA bases. Genome Res. 2012; 23(1):129-41. PMC: 3530673. DOI: 10.1101/gr.136739.111. View

15.

Garcia-del Portillo F, Pucciarelli M, Casadesus J . DNA adenine methylase mutants of Salmonella typhimurium show defects in protein secretion, cell invasion, and M cell cytotoxicity. Proc Natl Acad Sci U S A. 1999; 96(20):11578-83. PMC: 18076. DOI: 10.1073/pnas.96.20.11578. View

16.

Robertson K . DNA methylation and human disease. Nat Rev Genet. 2005; 6(8):597-610. DOI: 10.1038/nrg1655. View

17.

Casadesus J, Low D . Programmed heterogeneity: epigenetic mechanisms in bacteria. J Biol Chem. 2013; 288(20):13929-13935. PMC: 3656251. DOI: 10.1074/jbc.R113.472274. View

18.

Peterson S, Reich N . GATC flanking sequences regulate Dam activity: evidence for how Dam specificity may influence pap expression. J Mol Biol. 2005; 355(3):459-72. DOI: 10.1016/j.jmb.2005.11.003. View

19.

Wallecha A, Munster V, Correnti J, Chan T, van der Woude M . Dam- and OxyR-dependent phase variation of agn43: essential elements and evidence for a new role of DNA methylation. J Bacteriol. 2002; 184(12):3338-47. PMC: 135096. DOI: 10.1128/JB.184.12.3338-3347.2002. View

20.

Laszlo A, Derrington I, Ross B, Brinkerhoff H, Adey A, Nova I . Decoding long nanopore sequencing reads of natural DNA. Nat Biotechnol. 2014; 32(8):829-33. PMC: 4126851. DOI: 10.1038/nbt.2950. View