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Nat Commun. 2018 Feb 22;9(1):781. doi: 10.1038/s41467-018-03149-4.

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

Author information

1
Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, UK. stephen.clark@babraham.ac.uk.
2
European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge, CB10 1SD, UK.
3
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, CB2 0RE, UK.
4
School of Informatics, University of Edinburgh, Scotland, EH8 9AB, UK.
5
Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, UK.
6
Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
7
School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, 2308, Australia.
8
Bioinformatics Group, Babraham Institute, Cambridge, CB22 3AT, UK.
9
Centre for Trophoblast Research, University of Cambridge, Cambridge, CB2 3EG, UK.
10
European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge, CB10 1SD, UK. marioni@ebi.ac.uk.
11
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, CB2 0RE, UK. marioni@ebi.ac.uk.
12
Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK. marioni@ebi.ac.uk.
13
European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge, CB10 1SD, UK. oliver.stegle@ebi.ac.uk.
14
Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, UK. wolf.reik@babraham.ac.uk.
15
Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK. wolf.reik@babraham.ac.uk.
16
Centre for Trophoblast Research, University of Cambridge, Cambridge, CB2 3EG, UK. wolf.reik@babraham.ac.uk.

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.

PMID:
29472610
PMCID:
PMC5823944
DOI:
10.1038/s41467-018-03149-4
[Indexed for MEDLINE]
Free PMC Article

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