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

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

doi:10.1101/138685

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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.

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