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dc.contributor.authorSpiegel, Jochenen
dc.contributor.authorCuesta, Sergio Martínezen
dc.contributor.authorAdhikari, Santoshen
dc.contributor.authorHänsel-Hertsch, Roberten
dc.contributor.authorTannahill, Daviden
dc.contributor.authorBalasubramanian, Shankaren
dc.date.accessioned2021-03-27T00:30:45Z
dc.date.available2021-03-27T00:30:45Z
dc.date.issued2021-04-23en
dc.identifier.issn1474-7596
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/319278
dc.description.abstractBackground: 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
dc.description.sponsorshipEU H2020 Framework Programme (H2020-MSCA- IF-2016, ID: 747297-QAPs)
dc.format.mediumElectronicen
dc.languageengen
dc.publisherBioMed Central
dc.rightsAll rights reserved
dc.titleG-quadruplexes are transcription factor binding hubs in human chromatin.en
dc.typeArticle
prism.issueIdentifier1en
prism.publicationDate2021en
prism.publicationNameGenome biologyen
prism.startingPage117
prism.volume22en
dc.identifier.doi10.17863/CAM.66396
dcterms.dateAccepted2021-03-24en
rioxxterms.versionofrecord10.1186/s13059-021-02324-zen
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2021-04-23en
dc.contributor.orcidSpiegel, Jochen [0000-0001-7641-1066]
dc.contributor.orcidAdhikari, Santosh [0000-0002-1501-2106]
dc.contributor.orcidTannahill, David [0000-0002-3811-6864]
dc.contributor.orcidBalasubramanian, Shankar [0000-0002-0281-5815]
dc.identifier.eissn1474-760X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (CB4330)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (747297)
pubs.funder-project-idWellcome Trust (209441/Z/17/Z)
cam.orpheus.counter6*
rioxxterms.freetoread.startdate2024-03-26


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