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.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Hänsel-Hertsch R,Beraldi D,Lensing SV,Marsico G,Zyner K,Parry A,Di Antonio M,Pike J,Kimura H,Narita M,Tannahill D,Balasubramanian Sdoi
10.1038/ng.3662subject
Has Abstractpub_date
2016-10-01 00:00:00pages
1267-72issue
10eissn
1061-4036issn
1546-1718pii
ng.3662journal_volume
48pub_type
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