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

Stephen J Clark, Ricard Argelaguet, Andreas Kapourani, Thomas M Stubbs, Heather J Lee, Celia Alda-Catalinas, Felix Krueger, Guido Sanguinetti, Gavin Kelsey, John C Marioni, Oliver Stegle, Wolf Reik

Research output: Contribution to journalArticlepeer-review

Abstract

Parallel single-cell sequencing protocols represent powerful methods for investigating regulatory relationships, including epigenome-transcriptome interactions. Here, we report a novel 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.
Original languageEnglish
Article number781
Number of pages17
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 22 Feb 2018

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