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scNMT-seq enables joint profiling of chromatin accessibility DNA methylation and transcription in single cells.

Published version
Peer-reviewed

Type

Article

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Authors

Argelaguet, Ricard 
Kapourani, Chantriolnt-Andreas  ORCID logo  https://orcid.org/0000-0003-2303-1953
Stubbs, Thomas M 
Lee, Heather J 

Abstract

Parallel single-cell sequencing protocols represent powerful methods for investigating regulatory relationships, including epigenome-transcriptome interactions. Here, we report a single-cell method for parallel chromatin accessibility, DNA methylation and transcriptome profiling. scNMT-seq (single-cell nucleosome, methylation and transcription sequencing) uses a GpC methyltransferase to label open chromatin followed by bisulfite and RNA sequencing. We validate scNMT-seq by applying it to differentiating mouse embryonic stem cells, finding links between all three molecular layers and revealing dynamic coupling between epigenomic layers during differentiation.

Description

Keywords

Animals, Cell Differentiation, Chromatin, DNA Methylation, Embryonic Stem Cells, Female, Histones, Male, Mice, Nucleosomes, Sequence Analysis, DNA, Single-Cell Analysis, Transcription, Genetic

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

9

Publisher

Springer Science and Business Media LLC
Sponsorship
Biotechnology and Biological Sciences Research Council (1645504)
Cancer Research UK (22231)
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