Title | Simultaneous profiling of chromatin accessibility and methylation on human cell lines with nanopore sequencing. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Lee, I, Razaghi, R, Gilpatrick, T, Molnar, M, Gershman, A, Sadowski, N, Sedlazeck, FJ, Hansen, KD, Simpson, JT, Timp, W |
Journal | Nat Methods |
Volume | 17 |
Issue | 12 |
Pagination | 1191-1199 |
Date Published | 2020 Dec |
ISSN | 1548-7105 |
Keywords | Breast 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 |
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. |
DOI | 10.1038/s41592-020-01000-7 |
Alternate Journal | Nat Methods |
PubMed ID | 33230324 |
PubMed Central ID | PMC7704922 |
Grant List | R01 HG009190 / HG / NHGRI NIH HHS / United States T32 GM007057 / GM / NIGMS NIH HHS / United States T32 GM136577 / GM / NIGMS NIH HHS / United States |
Simultaneous profiling of chromatin accessibility and methylation on human cell lines with nanopore sequencing.
Similar Publications
Deep sequencing of candidate genes identified 14 variants associated with smoking abstinence in an ethnically diverse sample. Sci Rep. 2024;14(1):6385. | .
FAIR Header Reference genome: a TRUSTworthy standard. Brief Bioinform. 2024;25(3). | .
Gut Microbiota and Blood Metabolites Related to Fiber Intake and Type 2 Diabetes. Circ Res. 2024;134(7):842-854. | .