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

Nature Communications
Stephen J ClarkWolf Reik

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.

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Datasets Mentioned

BETA
GSE109262

Methods Mentioned

BETA
RNA-seq
BS-seq
scBS-seq
ChIP-seq
PCR

Software Mentioned

pseudotime
NOMe
R
HiSat2
scran
seq2
scNMT
destiny
Bismark
Smart

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