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• W3194657369 abstract "G-quadruplexes (G4s) are noncanonical DNA secondary structures formed through the self-association of guanines, and G4s are distributed widely across the genome. G4 participates in multiple biological processes including gene transcription, and G4-targeted ligands serve as potential therapeutic agents for DNA-targeted therapies. However, genome-wide studies of the exact roles of G4s in transcriptional regulation are still lacking. Here, we establish a sensitive G4-CUT&Tag method for genome-wide profiling of native G4s with high resolution and specificity. We find that native G4 signals are cell type-specific and are associated with transcriptional regulatory elements carrying active epigenetic modifications. Drug-induced promoter-proximal RNA polymerase II pausing promotes nearby G4 formation. In contrast, G4 stabilization by G4-targeted ligands globally reduces RNA polymerase II occupancy at gene promoters as well as nascent RNA synthesis. Moreover, ligand-induced G4 stabilization modulates chromatin states and impedes transcription initiation via inhibition of general transcription factors loading to promoters. Together, our study reveals a reciprocal genome-wide regulation between native G4 dynamics and gene transcription, which will deepen our understanding of G4 biology toward therapeutically targeting G4s in human diseases." @default.
• W3194657369 created "2021-08-30" @default.
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• W3194657369 date "2021-08-16" @default.
• W3194657369 modified "2023-10-18" @default.
• W3194657369 title "Ligand-induced native G-quadruplex stabilization impairs transcription initiation" @default.
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• W3194657369 doi "https://doi.org/10.1101/gr.275431.121" @default.
• W3194657369 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8415369" @default.
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• W3194657369 hasPublicationYear "2021" @default.
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