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| Status |
Public on Jul 16, 2018 |
| Title |
G-quadruplex structures moulds the DNA methylome |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Control of DNA methylation level is critical for gene regulation, and the factors that govern hypomethylation at CpG islands (CGIs) are still being uncovered. Here, we provide evidence that G-quadruplex (G4) DNA secondary structures are genomic features that influence methylation at CGIs. We show that the presence of G4 structure is tightly associated with CGI hypomethylation. Surprisingly, we find that these G4 sites are enriched for DNA methyltransferase 1 (DNMT1) occupancy, which is consistent with our biophysical observations that DNMT1 exhibits higher binding affinity for G4s as compared to duplex, hemi-methylated or single-stranded DNA. The biochemical assays also show that the G4 structure itself, rather than sequence, inhibits DNMT1 enzymatic activity. Based on these data, we propose that G4 formation sequesters DNMT1 thereby protecting certain CGIs from methylation and inhibiting local methylation.
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| Overall design |
G4 ChIP-seq perform on asynchronous K562 cells to detect the presence of DNA G-Quadruplexes. Experiment performed in 2 biological replicatest with 2 and 3 technical replicates, respectively. WGBS was done in entinostat treated HaCaT cells and control cells.
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| Contributor(s) |
Spiegel J, Ghanbarian A, Marsico G, Beraldi D, Hänsel-Hertsch R, Mao S, Tannahill D, Balasubramanian S |
| Citation(s) |
30275516, 33892767, 34183817 |
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| Submission date |
Dec 05, 2017 |
| Last update date |
Jul 20, 2021 |
| Contact name |
Avazeh T Ghanbarian |
| Organization name |
University of Cambridge
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| Department |
Cancer Research UK, Cambridge Inst
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| Lab |
Balasubramanian
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| Street address |
Robinson Way
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| City |
Cambridge |
| ZIP/Postal code |
CB2 0RE |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA421087 |
| SRA |
SRP126139 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE107690_K562_High_confidence_peaks.bed.gz |
73.9 Kb |
(ftp)(http) |
BED |
| GSE107690_RAW.tar |
3.2 Gb |
(http)(custom) |
TAR (of BW, NARROWPEAK, TDF) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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