Cited by 370Epigenetics and DNA MethylationRNA modifications and cancerBacterial Genetics and Biotechnology

Genome-wide mapping of methylated adenine residues in pathogenic Escherichia coli using single-molecule real-time sequencing

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Fang, Gang, Munera, Diana, Friedman, David I, Mandlik, Anjali, Chao, Michael C, Banerjee, Onureena, Feng, Zhixing, Losic, Bojan +15 more·2012·Nature Biotechnology

Abstract

Single-molecule real-time (SMRT) DNA sequencing allows the systematic detection of chemical modifications such as methylation but has not previously been applied on a genome-wide scale. We used this approach to detect 49,311 putative 6-methyladenine (m6A) residues and 1,407 putative 5-methylcytosine (m5C) residues in the genome of a pathogenic Escherichia coli strain. We obtained strand-specific information for methylation sites and a quantitative assessment of the frequency of methylation at each modified position. We deduced the sequence motifs recognized by the methyltransferase enzymes present in this strain without prior knowledge of their specificity. Furthermore, we found that deletion of a phage-encoded methyltransferase-endonuclease (restriction-modification; RM) system induced global transcriptional changes and led to gene amplification, suggesting that the role of RM systems extends beyond protecting host genomes from foreign DNA.

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Authors
Fang, G., Munera, D., Friedman, D. I., Mandlik, A., Chao, M. C., Banerjee, O., Feng, Z., Losic, B., Mahajan, M. C., Jabado, O. J., Deikus, G., Clark, T. A., Luong, K., Murray, I. A., Davis, B. M., Keren-Paz, A., Chess, A., Roberts, R. J., Korlach, J., Turner, S. W., Kumar, V., Waldor, M. K., & Schadt, E. E.
Affiliations
  • University of Minnesota (US)
  • Brigham and Women's Hospital (US)
  • University of Michigan (US)
  • Pacific Biosciences (United States) (US)
  • Stanford University (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • New England Biolabs (United States) (US)
Corresponding author
  • Waldor, Matthew K
  • Schadt, Eric E
Venue
Nature Biotechnology
Published
2012-11-08
Volume
30
Issue
12
Pages
1232-1239
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W2025361601
Cited by
360
References
51
Citations by year
2026: 7 · 2025: 21 · 2024: 19 · 2023: 19 · 2022: 24 · 2021: 24 · 2020: 29 · 2019: 30 · 2018: 36 · 2017: 19 · 2016: 25 · 2015: 44 · 2014: 31 · 2013: 25 · 2012: 4
FWCI
13.38
Type
journal article
Language
en
Update notices
erratum (2013-06-10)
Open access
Locations
  • Nature Biotechnology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation (0916439)
  • Howard Hughes Medical Institute
  • National Institutes of Health
  • National Institute of General Medical Sciences (R44GM100560, R44GM105125)
  • National Institute of Allergy and Infectious Diseases (R37AI-42347, R37AI042347)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
DNA methylation, 6-methyladenine, 5-methylcytosine, Escherichia coli, single-molecule real-time sequencing, restriction-modification systems, gene amplification, gene expression changes, genome-wide methylation mapping
MeSH terms
Adenine, Biotechnology, Chromosome Mapping, DNA, Bacterial, Escherichia coli, Gene Amplification, Spiro Compounds, Substrate Specificity, DNA Restriction-Modification Enzymes, Genome, Bacterial, Gene Deletion, Sequence Analysis, DNA, DNA Methylation, 5-Methylcytosine

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