G-quadruplexes are transcription factor binding hubs in human chromatin.
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Peer-reviewed
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Abstract
BACKGROUND: The binding of transcription factors (TF) to genomic targets is critical in the regulation of gene expression. Short, double-stranded DNA sequence motifs are routinely implicated in TF recruitment, but many questions remain on how binding site specificity is governed. RESULTS: Herein, we reveal a previously unappreciated role for DNA secondary structures as key features for TF recruitment. In a systematic, genome-wide study, we discover that endogenous G-quadruplex secondary structures (G4s) are prevalent TF binding sites in human chromatin. Certain TFs bind G4s with affinities comparable to double-stranded DNA targets. We demonstrate that, in a chromatin context, this binding interaction is competed out with a small molecule. Notably, endogenous G4s are prominent binding sites for a large number of TFs, particularly at promoters of highly expressed genes. CONCLUSIONS: Our results reveal a novel non-canonical mechanism for TF binding whereby G4s operate as common binding hubs for many different TFs to promote increased transcription.
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1474-760X
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European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (747297)
Wellcome Trust (209441/Z/17/Z)
Cancer Research UK (19836)
Cancer Research UK (C9681/A29214)