Clark Stephen J, Argelaguet Ricard, Kapourani Chantriolnt-Andreas, Stubbs Thomas M, Lee Heather J, Alda-Catalinas Celia, Krueger Felix, Sanguinetti Guido, Kelsey Gavin, Marioni John C, Stegle Oliver, Reik Wolf
Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, UK.
European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge, CB10 1SD, UK.
Nat Commun. 2018 Feb 22;9(1):781. 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 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.
平行单细胞测序方案是研究调控关系（包括表观基因组-转录组相互作用）的强大方法。在此，我们报告一种用于平行染色质可及性、DNA甲基化和转录组分析的单细胞方法。scNMT-seq（单细胞核小体、甲基化和转录测序）使用一种GpC甲基转移酶标记开放染色质，随后进行亚硫酸氢盐测序和RNA测序。我们将scNMT-seq应用于分化中的小鼠胚胎干细胞来验证该方法，发现了所有三个分子层之间的联系，并揭示了分化过程中表观基因组层之间的动态偶联。
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