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G-quadruplex DNA structures in human stem cells and differentiation

Author

Listed:
  • Katherine G. Zyner

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way)

  • Angela Simeone

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way)

  • Sean M. Flynn

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way)

  • Colm Doyle

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way)

  • Giovanni Marsico

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way)

  • Santosh Adhikari

    (University of Cambridge, Lensfield Road)

  • Guillem Portella

    (University of Cambridge, Lensfield Road)

  • David Tannahill

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way)

  • Shankar Balasubramanian

    (Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way
    University of Cambridge, Lensfield Road
    University of Cambridge)

Abstract

The establishment of cell identity during embryonic development involves the activation of specific gene expression programmes and is underpinned by epigenetic factors including DNA methylation and histone post-translational modifications. G-quadruplexes are four-stranded DNA secondary structures (G4s) that have been implicated in transcriptional regulation and cancer. Here, we show that G4s are key genomic structural features linked to cellular differentiation. We find that G4s are highly abundant in human embryonic stem cells and are lost during lineage specification. G4s are prevalent in enhancers and promoters. G4s that are found in common between embryonic and downstream lineages are tightly linked to transcriptional stabilisation of genes involved in essential cellular functions as well as transitions in the histone post-translational modification landscape. Furthermore, the application of small molecules that stabilise G4s causes a delay in stem cell differentiation, keeping cells in a more pluripotent-like state. Collectively, our data highlight G4s as important epigenetic features that are coupled to stem cell pluripotency and differentiation.

Suggested Citation

  • Katherine G. Zyner & Angela Simeone & Sean M. Flynn & Colm Doyle & Giovanni Marsico & Santosh Adhikari & Guillem Portella & David Tannahill & Shankar Balasubramanian, 2022. "G-quadruplex DNA structures in human stem cells and differentiation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27719-1
    DOI: 10.1038/s41467-021-27719-1
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    References listed on IDEAS

    as
    1. Jesse R. Dixon & Inkyung Jung & Siddarth Selvaraj & Yin Shen & Jessica E. Antosiewicz-Bourget & Ah Young Lee & Zhen Ye & Audrey Kim & Nisha Rajagopal & Wei Xie & Yarui Diao & Jing Liang & Huimin Zhao , 2015. "Chromatin architecture reorganization during stem cell differentiation," Nature, Nature, vol. 518(7539), pages 331-336, February.
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