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Simultaneous profiling of histone modifications and DNA methylation via nanopore sequencing

Author

Listed:
  • Xue Yue

    (Tongji University)

  • Zhiyuan Xie

    (Tongji University)

  • Moran Li

    (Tongji University)

  • Kai Wang

    (Tongji University)

  • Xiaojing Li

    (Tongji University)

  • Xiaoqing Zhang

    (Tongji University
    Tongji University
    Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital)

  • Jian Yan

    (School of Medicine, Northwest University
    City University of Hong Kong, Kowloon)

  • Yimeng Yin

    (Tongji University
    Tongji University)

Abstract

The interplay between histone modifications and DNA methylation drives the establishment and maintenance of the cellular epigenomic landscape, but it remains challenging to investigate the complex relationship between these epigenetic marks across the genome. Here we describe a nanopore-sequencing-based-method, nanoHiMe-seq, for interrogating the genome-wide localization of histone modifications and DNA methylation from single DNA molecules. nanoHiMe-seq leverages a nonspecific methyltransferase to exogenously label adenine bases proximal to antibody-targeted modified nucleosomes in situ. The labelled adenines and the endogenous methylated CpG sites are simultaneously detected on individual nanopore reads using a hidden Markov model, which is implemented in the nanoHiMe software package. We demonstrate the utility, robustness and sensitivity of nanoHiMe-seq by jointly profiling DNA methylation and histone modifications at low coverage depths, concurrently determining phased patterns of DNA methylation and histone modifications, and probing the intrinsic connectivity between these epigenetic marks across the genome.

Suggested Citation

  • Xue Yue & Zhiyuan Xie & Moran Li & Kai Wang & Xiaojing Li & Xiaoqing Zhang & Jian Yan & Yimeng Yin, 2022. "Simultaneous profiling of histone modifications and DNA methylation via nanopore sequencing," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35650-2
    DOI: 10.1038/s41467-022-35650-2
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    1. Ryan Lister & Mattia Pelizzola & Robert H. Dowen & R. David Hawkins & Gary Hon & Julian Tonti-Filippini & Joseph R. Nery & Leonard Lee & Zhen Ye & Que-Minh Ngo & Lee Edsall & Jessica Antosiewicz-Bourg, 2009. "Human DNA methylomes at base resolution show widespread epigenomic differences," Nature, Nature, vol. 462(7271), pages 315-322, November.
    2. Zaka Wing-Sze Yuen & Akanksha Srivastava & Runa Daniel & Dennis McNevin & Cameron Jack & Eduardo Eyras, 2021. "Systematic benchmarking of tools for CpG methylation detection from nanopore sequencing," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
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