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

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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, Mahajan, Milind C, Jabado, Omar J, Deikus, Gintaras, Clark, Tyson A, Luong, Khai, Murray, Iain A, Davis, Brigid M, Keren-Paz, Alona, Chess, Andrew, Roberts, Richard J, Korlach, Jonas, Turner, Steve W, Kumar, Vipin, Waldor, Matthew K, Schadt, Eric E·2012·Nature Biotechnology

DOI 10.1038/nbt.2432PMC PMC3879109

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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
ORCID: Fang, Gang
Friedman, David I
Chao, Michael C
Feng, Zhixing
Losic, Bojan
Deikus, Gintaras
Clark, Tyson A
Murray, Iain A
Chess, Andrew
Roberts, Richard J
Korlach, Jonas
Turner, Steve W
Kumar, Vipin
Waldor, Matthew K
Schadt, Eric E
Venue: Nature Biotechnology
Publisher: Springer Science and Business Media LLC
Published: 2012-11-08
Volume: 30
Issue: 12
Pages: 1232-1239
ISSN: 0733-222X (ISSN-L)
1087-0156
1546-1696
DOI: 10.1038/nbt.2432
PMC: PMC3879109
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: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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Genome-wide mapping of methylated adenine residues in pathogenic Escherichia coli using single-molecule real-time sequencing

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