4.8 Article

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

Journal

NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-03149-4

Keywords

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Funding

  1. Biotechnology and Biological Sciences Research Council (BBSRC)
  2. Wellcome Trust
  3. EU Blueprint
  4. EpiGeneSys
  5. BBSRC
  6. Medical Research Council (MRC)
  7. European Molecular Biology Laboratory (EMBL)
  8. EU
  9. EPSRC Centre for Doctoral Training in Data Science [EP/L016427/1]
  10. University of Edinburgh
  11. Wellcome Trust [105031/Z/14/Z] Funding Source: Wellcome Trust
  12. BBSRC [BBS/E/B/000C0422, 1645504, BBS/E/B/000C0426, BBS/E/B/0000H334] Funding Source: UKRI
  13. MRC [MR/K011332/1] Funding Source: UKRI
  14. Biotechnology and Biological Sciences Research Council [BBS/E/B/0000H334, 1645504, BBS/E/B/000C0422, BBS/E/B/000C0426] Funding Source: researchfish
  15. Cancer Research UK [22231] Funding Source: researchfish
  16. Engineering and Physical Sciences Research Council [1497322] Funding Source: researchfish
  17. Medical Research Council [MR/K011332/1] Funding Source: researchfish
  18. Wellcome Trust [105031/Z/14/Z] Funding Source: researchfish

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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.

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