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Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation

Author

Listed:
  • Hemalvi Patani

    (Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London)

  • Michael D. Rushton

    (Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London)

  • Jonathan Higham

    (MRC Human Genetics Unit and Edinburgh Cancer Research Centre, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, Western General Hospital)

  • Saul A. Teijeiro

    (Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London)

  • David Oxley

    (Mass Spectrometry Facility, Babraham Institute)

  • Pedro Cutillas

    (Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London)

  • Duncan Sproul

    (MRC Human Genetics Unit and Edinburgh Cancer Research Centre, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, Western General Hospital)

  • Gabriella Ficz

    (Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London)

Abstract

Epigenetic reprogramming is a cancer hallmark, but how it unfolds during early neoplastic events and its role in carcinogenesis and cancer progression is not fully understood. Here we show that resetting from primed to naïve human pluripotency results in acquisition of a DNA methylation landscape mirroring the cancer DNA methylome, with gradual hypermethylation of bivalent developmental genes. We identify a dichotomy between bivalent genes that do and do not become hypermethylated, which is also mirrored in cancer. We find that loss of H3K4me3 at bivalent regions is associated with gain of methylation. Additionally, we observe that promoter CpG island hypermethylation is not restricted solely to emerging naïve cells, suggesting that it is a feature of a heterogeneous intermediate population during resetting. These results indicate that transition to naïve pluripotency and oncogenic transformation share common epigenetic trajectories, which implicates reprogramming and the pluripotency network as a central hub in cancer formation.

Suggested Citation

  • Hemalvi Patani & Michael D. Rushton & Jonathan Higham & Saul A. Teijeiro & David Oxley & Pedro Cutillas & Duncan Sproul & Gabriella Ficz, 2020. "Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17269-3
    DOI: 10.1038/s41467-020-17269-3
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