Simultaneous profiling of histone modifications and DNA methylation via nanopore sequencing

Xue Yue, Zhiyuan Xie, Moran Li, Kai Wang, Xiaojing Li, Xiaoqing Zhang, Jian Yan and Yimeng Yin ()
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Xue Yue: Tongji University
Zhiyuan Xie: Tongji University
Moran Li: Tongji University
Kai Wang: Tongji University
Xiaojing Li: Tongji University
Xiaoqing Zhang: Tongji University
Jian Yan: School of Medicine, Northwest University
Yimeng Yin: Tongji University

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-35650-2

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