G-quadruplex structures mark human regulatory chromatin.

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 Genet

journal_title

Nature genetics

authors

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 S

doi

10.1038/ng.3662

subject

Has Abstract

pub_date

2016-10-01 00:00:00

pages

1267-72

issue

10

eissn

1061-4036

issn

1546-1718

pii

ng.3662

journal_volume

48

pub_type

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