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DNA unmethylome profiling by covalent capture of CpG sites

Author

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  • Edita Kriukienė

    (Institute of Biotechnology, Vilnius University)

  • Viviane Labrie

    (The Krembil Family Epigenetics Laboratory, The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health)

  • Tarang Khare

    (The Krembil Family Epigenetics Laboratory, The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health)

  • Giedrė Urbanavičiūtė

    (Institute of Biotechnology, Vilnius University)

  • Audronė Lapinaitė

    (Institute of Biotechnology, Vilnius University
    Present address: European Molecular Biology Laboratory, Heidelberg, Germany)

  • Karolis Koncevičius

    (Faculty of Mathematics and Informatics, Vilnius University)

  • Daofeng Li

    (Centre for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Ting Wang

    (Centre for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Shraddha Pai

    (The Krembil Family Epigenetics Laboratory, The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health)

  • Carolyn Ptak

    (The Krembil Family Epigenetics Laboratory, The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health)

  • Juozas Gordevičius

    (Institute of Mathematics and Informatics, Vilnius University)

  • Sun-Chong Wang

    (Institute of Systems Biology and Bioinformatics, National Central University)

  • Artūras Petronis

    (The Krembil Family Epigenetics Laboratory, The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health)

  • Saulius Klimašauskas

    (Institute of Biotechnology, Vilnius University)

Abstract

Dynamic patterns of cytosine-5 methylation and successive hydroxylation are part of epigenetic regulation in eukaryotes, including humans, which contributes to normal phenotypic variation and disease risk. Here we present an approach for the mapping of unmodified regions of the genome, which we call the unmethylome. Our technique is based on DNA methyltransferase-directed transfer of activated groups and covalent biotin tagging of unmodified CpG sites followed by affinity enrichment and interrogation on tiling microarrays or next generation sequencing. Control experiments and pilot studies of human genomic DNA from cultured cells and tissues demonstrate that, along with providing a unique cross-section through the chemical landscape of the epigenome, the methyltransferase-directed transfer of activated groups-based approach offers high precision and robustness as compared with existing affinity-based techniques.

Suggested Citation

  • Edita Kriukienė & Viviane Labrie & Tarang Khare & Giedrė Urbanavičiūtė & Audronė Lapinaitė & Karolis Koncevičius & Daofeng Li & Ting Wang & Shraddha Pai & Carolyn Ptak & Juozas Gordevičius & Sun-Chong, 2013. "DNA unmethylome profiling by covalent capture of CpG sites," Nature Communications, Nature, vol. 4(1), pages 1-10, October.
  • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3190
    DOI: 10.1038/ncomms3190
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