» Articles » PMID: 33962653

Promoter G-quadruplex Folding Precedes Transcription and is Controlled by Chromatin

Overview
Journal Genome Biol
Specialties Biology
Genetics
Date 2021 May 8
PMID 33962653
Citations 46
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Gene regulation by convergent promoters.

Wiechens E, Vigliotti F, Siniuk K, Schwarz R, Schwab K, Riege K Nat Genet. 2025; 57(1):206-217.

PMID: 39779959 PMC: 11735407. DOI: 10.1038/s41588-024-02025-w.


Base Excision Repair in Mitotic Cells and the Role of Apurinic/Apyrimidinic Endonuclease 1 (APE1) in Post-Mitotic Transcriptional Reactivation of Genes.

Pramanik S, Chen Y, Bhakat K Int J Mol Sci. 2024; 25(23).

PMID: 39684445 PMC: 11641725. DOI: 10.3390/ijms252312735.


A Compendium of G-Flipon Biological Functions That Have Experimental Validation.

Herbert A Int J Mol Sci. 2024; 25(19).

PMID: 39408629 PMC: 11477331. DOI: 10.3390/ijms251910299.


Untargeted CUT&Tag and BG4 CUT&Tag are both enriched at G-quadruplexes and accessible chromatin.

Thompson M, Byrd A bioRxiv. 2024; .

PMID: 39386625 PMC: 11463444. DOI: 10.1101/2024.09.26.615263.


Improved simultaneous mapping of epigenetic features and 3D chromatin structure via ViCAR.

Flynn S, Dhir S, Herka K, Doyle C, Melidis L, Simeone A Genome Biol. 2024; 25(1):237.

PMID: 39227991 PMC: 11370281. DOI: 10.1186/s13059-024-03377-6.


References
1.
Bristow R, Hill R . Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer. 2008; 8(3):180-92. DOI: 10.1038/nrc2344. View

2.
Hansel-Hertsch R, Simeone A, Shea A, Hui W, Zyner K, Marsico G . Landscape of G-quadruplex DNA structural regions in breast cancer. Nat Genet. 2020; 52(9):878-883. DOI: 10.1038/s41588-020-0672-8. View

3.
Kouzine F, Liu J, Sanford S, Chung H, Levens D . The dynamic response of upstream DNA to transcription-generated torsional stress. Nat Struct Mol Biol. 2004; 11(11):1092-100. DOI: 10.1038/nsmb848. View

4.
Balasubramanian S, Hurley L, Neidle S . Targeting G-quadruplexes in gene promoters: a novel anticancer strategy?. Nat Rev Drug Discov. 2011; 10(4):261-75. PMC: 3119469. DOI: 10.1038/nrd3428. View

5.
Varshney D, Vavrova-Anderson J, Oler A, Cowling V, Cairns B, White R . SINE transcription by RNA polymerase III is suppressed by histone methylation but not by DNA methylation. Nat Commun. 2015; 6:6569. PMC: 4382998. DOI: 10.1038/ncomms7569. View