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| Status |
Public on Jan 12, 2023 |
| Title |
Pan-cancer analysis revealed H3K4me1 at bivalent promoters premarks DNA hypermethylation during tumor development and identified the regulatory role of DNA methylation in relation to histone modifications [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Background: DNA hypermethylation at promoter CpG islands (CGIs) is a hallmark of cancers and could lead to dysregulation of gene expression in the development of cancers, however, its dynamics and regulatory mechanisms remain elusive. Bivalent genes, that direct development and differentiation of stem cells, are found to be frequent targets of hypermethylation in cancers.
Results: Here we performed comprehensive analysis across multiple cancer types and identified that the decrease in H3K4me1 levels coincides with DNA hypermethylation at the bivalent promoter CGIs during tumorigenesis. Removal of DNA hypermethylation leads to increment of H3K4me1 at promoter CGIs with preference for bivalent genes. Nevertheless, the alteration of H3K4me1 by overexpressing or knockout LSD1, the demethylase of H3K4, doesn't change the level or pattern of DNA methylation. Moreover, LSD1 was found to regulate the expression of a bivalent gene OVOL2 to promote tumorigenesis. Knockdown of OVOL2 in LSD1 knockout HCT116 cells restored the cancer cell phenotype.
Conclusion: In summary, our work identified a universal indicator that can pre-mark DNA hypermethylation in cancer cells, and dissected the interplay between H3K4me1 and DNA hypermethylation in detail. Current study also reveals a novel mechanism underlying the oncogenic role of LSD1, providing clues for cancer therapies.
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| Overall design |
we performed comprehensive analysis across multiple cancer types and identified that DNA hypermethylation in cancers can be predicated by enriched unimodal pattern of Histone H3 lysine 4 mono-methylation (H3K4me1) in corresponding normal tissues.
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| Contributor(s) |
Lu Y, Cao Q, Jiang X, Li X |
| Citation(s) |
37138231 |
| |
| Submission date |
Jan 10, 2023 |
| Last update date |
May 14, 2023 |
| Contact name |
Cao Qiang |
| E-mail(s) |
csqasds@gmail.com
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| Organization name |
Sun Yat-sen University
|
| Department |
School of Medicine
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| Street address |
No. 66 Gongchang Road, Guangming District, Shenzhen
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| City |
Shenzhen |
| ZIP/Postal code |
518000 |
| Country |
China |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE222612 |
Pan-cancer analysis revealed H3K4me1 at bivalent promoters premarks DNA hypermethylation during tumor development and identified the regulatory role of DNA methylation in relation to histone modifications |
|
| Relations |
| BioProject |
PRJNA922465 |
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