Simultaneous profiling of chromatin accessibility and methylation on human cell lines with nanopore sequencing

Isac Lee, Roham Razaghi, Timothy Gilpatrick, Michael Molnar, Ariel Gershman, Norah Sadowski, Fritz J. Sedlazeck, Kasper D. Hansen, Jared T. Simpson, Winston Timp

Research output: Contribution to journalArticlepeer-review

Abstract

Probing epigenetic features on DNA has tremendous potential to advance our understanding of the phased epigenome. In this study, we use nanopore sequencing to evaluate CpG methylation and chromatin accessibility simultaneously on long strands of DNA by applying GpC methyltransferase to exogenously label open chromatin. We performed nanopore sequencing of nucleosome occupancy and methylome (nanoNOMe) on four human cell lines (GM12878, MCF-10A, MCF-7 and MDA-MB-231). The single-molecule resolution allows footprinting of protein and nucleosome binding, and determination of the combinatorial promoter epigenetic signature on individual molecules. Long-read sequencing makes it possible to robustly assign reads to haplotypes, allowing us to generate a fully phased human epigenome, consisting of chromosome-level allele-specific profiles of CpG methylation and chromatin accessibility. We further apply this to a breast cancer model to evaluate differential methylation and accessibility between cancerous and noncancerous cells.

Original languageEnglish (US)
Pages (from-to)1191-1199
Number of pages9
JournalNature Methods
Volume17
Issue number12
DOIs
StatePublished - Dec 2020

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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