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G-quadruplex structures mark human regulatory chromatin

Accepted version
Peer-reviewed

Type

Article

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Authors

Hänsel-Hertsch, R 
Beraldi, D 
Lensing, SV 
Marsico, G 
Zyner, K 

Abstract

G-quadruplex (G4) structural motifs have been linked to transcription, replication and genome instability and are implicated in cancer and other diseases. However, it is crucial to demonstrate the bona fide formation of G4 structures within an endogenous chromatin context. 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.

Description

Keywords

Cell Line, Chromatin, Chromatin Immunoprecipitation, G-Quadruplexes, High-Throughput Nucleotide Sequencing, Humans, Real-Time Polymerase Chain Reaction, Regulatory Sequences, Nucleic Acid, Transcription, Genetic

Journal Title

Nature Genetics

Conference Name

Journal ISSN

1061-4036
1546-1718

Volume Title

48

Publisher

Nature Publishing Group
Sponsorship
Cancer Research UK (C14303/A17197)
Wellcome Trust (099232/Z/12/Z)
Cancer Research UK (CB4330)
Cancer Research UK (18618)
Cancer Research UK (19836)
Cancer Research UK (15890)
European Molecular Biology Organization (EMBO Long-Term Fellowship), University of Cambridge, Cancer Research UK (Grant ID: C14303/A17197), Wellcome Trust (Grant ID: 099232/z/12/z)