Simultaneous profiling of histone modifications and DNA methylation via nanopore sequencing

Nature Communications, 2022 · DOI: 10.1038/s41467-022-35650-2 · Published: December 15, 2022

Simple Explanation

The study introduces nanoHiMe-seq, a novel nanopore sequencing method, to simultaneously profile histone modifications and DNA methylation. This method uses a methyltransferase to label adenine bases near modified nucleosomes, allowing for the concurrent detection of these labels and endogenous methylated CpG sites. The utility of nanoHiMe-seq is demonstrated through joint profiling of DNA methylation and histone modifications, determining phased patterns, and probing the connectivity between these epigenetic marks.

Study Duration

Not specified

Participants

HepG2 and GM12878 cell lines

Evidence Level

Not specified

Key Findings

1
nanoHiMe-seq allows for the simultaneous profiling of CpG methylation and histone modifications, exhibiting utility, robustness, and sensitivity.
2
The method can identify allele-specific epigenetic states across the genome and probe the intrinsic connectivity between epigenetic marks along multikilobase segments.
3
nanoHiMe-seq precisely maps histone modifications in both compacted and open chromatin.

Research Summary

The study introduces nanoHiMe-seq, a nanopore-sequencing-based method for interrogating the genome-wide localization of histone modifications and DNA methylation from single DNA molecules. nanoHiMe-seq leverages a nonspecifc 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.

Practical Implications

Epigenetic Research

nanoHiMe-seq provides a valuable tool for studying the functional coordination of epigenetic marks in various biological contexts.

Chromatin Studies

The method is suitable for investigating chromatin features in complex genomic regions due to its long reads and no-amplification strategy.

Drug Discovery

The ability to simultaneously profile histone modifications and DNA methylation could aid in understanding drug responses and developing targeted therapies.

Study Limitations

1
The method loses the ability to predict adenine methylation at base resolution.
2
The technique relies on antibody specificity for targeting modified nucleosomes.
3
Extensive training models are required to explore multiple chromatin features simultaneously.

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