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Promoter G-quadruplex folding precedes transcription and is controlled by chromatin

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Shen, Jiazhen 
Varshney, Dhaval 
Simeone, Angela 
Zhang, Xiaoyun 
Adhikari, Santosh 


Abstract: Background: Four-stranded G-quadruplexes (G4s) are DNA secondary structures in the human genome that are primarily found in active promoters associated with elevated transcription. Here, we explore the relationship between the folding of promoter G4s, transcription and chromatin state. Results: Transcriptional inhibition by DRB or by triptolide reveals that promoter G4 formation, as assessed by G4 ChIP-seq, does not depend on transcriptional activity. We then show that chromatin compaction can lead to loss of promoter G4s and is accompanied by a corresponding loss of RNA polymerase II (Pol II), thus establishing a link between G4 formation and chromatin accessibility. Furthermore, pre-treatment of cells with a G4-stabilising ligand mitigates the loss of Pol II at promoters induced by chromatin compaction. Conclusions: Overall, our findings show that G4 folding is coupled to the establishment of accessible chromatin and does not require active transcription.


Funder: Herchel Smith Funds


Research, G-quadruplexes, Transcription, RNA polymerase II, Chromatin compaction

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Genome Biology

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BioMed Central
Cancer Research UK (C9545/A19836)
Cancer Research UK (C9681/A29214)
Wellcome Trust (209441/Z/17/Z)