Chromatin Velocity reveals epigenetic dynamics by single-cell profiling of heterochromatin and euchromatin.

Chromatin / genetics Epigenesis, Genetic / genetics Euchromatin / genetics Heterochromatin / genetics Humans Transposases / genetics

Journal

Nature biotechnology

ISSN: 1546-1696

Titre abrégé: Nat Biotechnol

Pays: United States

ID NLM: 9604648

Informations de publication

Date de publication:
02 2022

Historique:

received: 05 10 2020

accepted: 22 07 2021

pubmed: 13 10 2021

medline: 22 4 2022

entrez: 12 10 2021

Statut: ppublish

Résumé

Recent efforts have succeeded in surveying open chromatin at the single-cell level, but high-throughput, single-cell assessment of heterochromatin and its underlying genomic determinants remains challenging. We engineered a hybrid transposase including the chromodomain (CD) of the heterochromatin protein-1α (HP-1α), which is involved in heterochromatin assembly and maintenance through its binding to trimethylation of the lysine 9 on histone 3 (H3K9me3), and developed a single-cell method, single-cell genome and epigenome by transposases sequencing (scGET-seq), that, unlike single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq), comprehensively probes both open and closed chromatin and concomitantly records the underlying genomic sequences. We tested scGET-seq in cancer-derived organoids and human-derived xenograft (PDX) models and identified genetic events and plasticity-driven mechanisms contributing to cancer drug resistance. Next, building upon the differential enrichment of closed and open chromatin, we devised a method, Chromatin Velocity, that identifies the trajectories of epigenetic modifications at the single-cell level. Chromatin Velocity uncovered paths of epigenetic reorganization during stem cell reprogramming and identified key transcription factors driving these developmental processes. scGET-seq reveals the dynamics of genomic and epigenetic landscapes underlying any cellular processes.

Identifiants

DOI: 10.1038/s41587-021-01031-1 PMID: 34635836

pubmed: 34635836

doi: 10.1038/s41587-021-01031-1

pii: 10.1038/s41587-021-01031-1

doi:

Substances chimiques

Chromatin 0

Euchromatin 0

Heterochromatin 0

Transposases EC 2.7.7.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

235-244

Subventions

Organisme : Cancer Research UK (CRUK)

ID : 22795

Commentaires et corrections

Type : CommentIn

Informations de copyright

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