G-quadruplex DNA structures in human stem cells and differentiation.
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Zyner, K. G., Simeone, A., Flynn, S. M., Doyle, C., Marsico, G., Adhikari, S., Portella, G., et al. (2022). G-quadruplex DNA structures in human stem cells and differentiation.. Nat Commun, 13 (1) https://doi.org/10.1038/s41467-021-27719-1
Funder: Herchel Smith Funds
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.
Cell Line, Pluripotent Stem Cells, Humans, Receptors, Nerve Growth Factor, Nerve Tissue Proteins, Histones, DNA, Cell Differentiation, DNA Methylation, Gene Expression, Epigenesis, Genetic, Protein Processing, Post-Translational, Cell Lineage, Transcription Factor AP-2, Octamer Transcription Factor-3, G-Quadruplexes, Enhancer Elements, Genetic, Promoter Regions, Genetic, Nestin, Biomarkers, Human Embryonic Stem Cells, PAX6 Transcription Factor, Nanog Homeobox Protein
Cancer Research UK (CB4330)
Cancer Research UK (C9681/A29214)
Wellcome Trust (209441/Z/17/Z)
External DOI: https://doi.org/10.1038/s41467-021-27719-1
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333955
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/