TY - JOUR
T1 - G-quadruplex structures mark human regulatory chromatin
AU - Hänsel-Hertsch, R
AU - Beraldi, D
AU - Lensing, SV
AU - Marsico, G
AU - Zyner, K
AU - Parry, A
AU - Di, Antonio M
AU - Pike, J
AU - Kimura, H
AU - Narita, M
AU - Tannahill, D
AU - Balasubramanian, S
PY - 2016/10
Y1 - 2016/10
N2 - 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.
AB - 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.
UR - http://europepmc.org/abstract/med/27618450
U2 - 10.1038/ng.3662
DO - 10.1038/ng.3662
M3 - Article
C2 - 27618450
SN - 1061-4036
VL - 48
SP - 1267
EP - 1272
JO - Nature Genetics
JF - Nature Genetics
IS - 10
ER -