Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation

Hemalvi Patani, Michael D. Rushton, Jonathan Higham, Saul A. Teijeiro, David Oxley, Pedro Cutillas, Duncan Sproul and Gabriella Ficz ()
Additional contact information
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

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-17269-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17269-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-17269-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().