Journal
GENOME BIOLOGY
Volume 22, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13059-021-02346-7
Keywords
G-quadruplexes; Transcription; RNA polymerase II; Chromatin compaction
Funding
- Cancer Research UK [C9545/A19836, C9681/A29214]
- Wellcome Trust [209441/Z/17/Z]
- Herchel Smith Funds
- Wellcome Trust [209441/Z/17/Z] Funding Source: Wellcome Trust
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The folding of G4s is linked to the establishment of accessible chromatin and does not require active transcription.
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.
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