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G-quadruplex DNA structures in human stem cells and differentiation.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Simeone, Angela 
Doyle, Colm 
Marsico, Giovanni 

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.

Description

Funder: Herchel Smith Funds

Keywords

Biomarkers, Cell Differentiation, Cell Line, Cell Lineage, DNA, DNA Methylation, Enhancer Elements, Genetic, Epigenesis, Genetic, G-Quadruplexes, Gene Expression, Histones, Human Embryonic Stem Cells, Humans, Nanog Homeobox Protein, Nerve Tissue Proteins, Nestin, Octamer Transcription Factor-3, PAX6 Transcription Factor, Pluripotent Stem Cells, Promoter Regions, Genetic, Protein Processing, Post-Translational, Receptors, Nerve Growth Factor, Transcription Factor AP-2

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

13

Publisher

Nature Research
Sponsorship
Cancer Research UK (CB4330)
Cancer Research UK (C9681/A29214)
Wellcome Trust (209441/Z/17/Z)
Cancer Research UK (19836)