Simultaneous profiling of chromatin accessibility and methylation on human cell lines with nanopore sequencing.
Breast Neoplasms
/ genetics
Cell Line, Tumor
Chromatin
/ genetics
CpG Islands
/ genetics
DNA
/ metabolism
DNA Methylation
/ genetics
Epigenome
/ genetics
Female
Genome, Human
/ genetics
Humans
MCF-7 Cells
Methyltransferases
/ metabolism
Nanopore Sequencing
/ methods
Promoter Regions, Genetic
/ genetics
Sequence Analysis, DNA
Journal
Nature methods
ISSN: 1548-7105
Titre abrégé: Nat Methods
Pays: United States
ID NLM: 101215604
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
15
02
2019
accepted:
17
10
2020
pubmed:
25
11
2020
medline:
9
2
2021
entrez:
24
11
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33230324
doi: 10.1038/s41592-020-01000-7
pii: 10.1038/s41592-020-01000-7
pmc: PMC7704922
mid: NIHMS1638772
doi:
Substances chimiques
Chromatin
0
DNA
9007-49-2
Methyltransferases
EC 2.1.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1191-1199Subventions
Organisme : NHGRI NIH HHS
ID : R01 HG009190
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007057
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM136577
Pays : United States
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