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

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

Posted 17 May 2017
bioRxiv DOI: 10.1101/138685 (published DOI: 10.1038/s41467-018-03149-4)

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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