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

TitleSimultaneous profiling of chromatin accessibility and methylation on human cell lines with nanopore sequencing.
Publication TypeJournal Article
Year of Publication2020
AuthorsLee, I, Razaghi, R, Gilpatrick, T, Molnar, M, Gershman, A, Sadowski, N, Sedlazeck, FJ, Hansen, KD, Simpson, JT, Timp, W
JournalNat Methods
Date Published2020 Dec
KeywordsBreast Neoplasms, Cell Line, Tumor, Chromatin, CpG Islands, DNA, DNA Methylation, Epigenome, Female, Genome, Human, Humans, MCF-7 Cells, Methyltransferases, Nanopore Sequencing, Promoter Regions, Genetic, Sequence Analysis, DNA

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.

Alternate JournalNat Methods
PubMed ID33230324
PubMed Central IDPMC7704922
Grant ListR01 HG009190 / HG / NHGRI NIH HHS / United States
T32 GM007057 / GM / NIGMS NIH HHS / United States
T32 GM136577 / GM / NIGMS NIH HHS / United States

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