G-quadruplex structures mark human regulatory chromatin
Open accessAbstract
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.
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The prevalence of G4s is significantly increased in immortalized cells compared to primary human cells.
“Furthermore, the prevalence of G4s was found to be significantly increased in immortalized cells as compared to primary human cells (13).”
From G-quadruplex-mediated genomic instability drives SNVs in cancer (2024) · cites this paper as [13]
The comparison on p. 5 reports 10,560 G4 ChIP-seq peaks in immortalized HaCaT cells versus 1,496 in normal human epidermal keratinocytes; the Figure 3 caption calls the increase significant. The source supports this specific cell-type comparison, but not a general increase across immortalized cells compared with primary human cells. (LLM, conf=0.83)
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- Authors
- Hänsel-Hertsch, R., Beraldi, D., Lensing, S. V., Marsico, G., Zyner, K., Parry, A., Di Antonio, M., Pike, J., Kimura, H., Narita, M., Tannahill, D., & Balasubramanian, S.
- Affiliations
- Cancer Research UK (GB)
- University of Cambridge (GB)
- Corresponding author
- Balasubramanian, Shankar
- ORCID
- Venue
- Nature Genetics
- Published
- 2016-09-12
- Volume
- 48
- Issue
- 10
- Pages
- 1267-1272
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2520749639
- Cited by
- 964
- References
- 7
- Citations by year
- 2026: 75 · 2025: 98 · 2024: 141 · 2023: 107 · 2022: 91 · 2021: 135 · 2020: 103 · 2019: 87 · 2018: 72 · 2017: 51 · 2016: 3
- FWCI
- 37.09
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Tokyo Tech Research Repository (Tokyo Institute of Technology) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo
- Funders
- Wellcome Trust (099232/Z/12/Z)
- Cancer Research UK (CB4330, 19836, C14303 / A17197, 18618, 15890)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- chromatin, nucleosome-depleted regions, promoter, 5' untranslated region, transcriptional regulation, chromatin immunoprecipitation, histone deacetylase inhibitors, chromatin relaxation, c-Myc, cancer genes, transcriptional activity
- MeSH terms
- Cell Line, Chromatin, Humans, Regulatory Sequences, Nucleic Acid, Transcription, Genetic, Chromatin Immunoprecipitation, G-Quadruplexes, High-Throughput Nucleotide Sequencing, Real-Time Polymerase Chain Reaction
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