G-quadruplex structures mark human regulatory chromatin

R Hänsel-Hertsch, D Beraldi, SV Lensing, G Marsico, K Zyner, A Parry, Antonio M Di, J Pike, H Kimura, M Narita, D Tannahill, S Balasubramanian

Research output: Contribution to journalArticlepeer-review

310 Citations (Scopus)

Abstract

G-quadruplex (G4) structural motifs have been linked to transcription1,2, replication3 and genome instability4,5 and are implicated in cancer and other diseases6,7,8. However, it is crucial to demonstrate the bona fide formation of G4 structures within an endogenous chromatin context9,10. Herein we address this through the development of G4 ChIP–seq, an antibody-based G4 chromatin immunoprecipitation and high-throughput sequencing approach. We find ∼10,000 G4 structures in human chromatin, predominantly in regulatory, nucleosome-depleted regions. G4 structures are enriched in the promoters and 5′ UTRs of highly transcribed genes, particularly in genes related to cancer and in somatic copy number amplifications, such as MYC. Strikingly, de novo and enhanced G4 formation are associated with increased transcriptional activity, as shown by HDAC inhibitor–induced chromatin relaxation and observed in immortalized as compared to normal cellular states. Our findings show that regulatory, nucleosome-depleted chromatin and elevated transcription shape the endogenous human G4 DNA landscape.
Original languageEnglish
Pages (from-to)1267–1272
Number of pages9
JournalNature Genetics
Volume48
Issue number10
Early online date12 Sep 2016
DOIs
Publication statusPublished - Oct 2016

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