PT - JOURNAL ARTICLE AU - Stephen J. Clark AU - Ricard Argelaguet AU - Chantriolnt-Andreas Kapourani AU - Thomas M. Stubbs AU - Heather J. Lee AU - Felix Krueger AU - Guido Sanguinetti AU - Gavin Kelsey AU - John C. Marioni AU - Oliver Stegle AU - Wolf Reik TI - Joint profiling of chromatin accessibility, DNA methylation and transcription in single cells AID - 10.1101/138685 DP - 2017 Jan 01 TA - bioRxiv PG - 138685 4099 - http://biorxiv.org/content/early/2017/05/17/138685.short 4100 - http://biorxiv.org/content/early/2017/05/17/138685.full AB - Parallel single-cell sequencing protocols represent powerful methods for investigating regulatory relationships, including epigenome-transcriptome interactions. Here, we report the first 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 mouse embryonic stem cells, finding links between all three molecular layers and revealing strong and widespread associations between chromatin accessibility and DNA methylation.