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| Status |
Public on Jun 27, 2022 |
| Title |
H3K27me3 shapes DNA methylome by inhibiting UHRF1-mediated H3 ubiquitination [Bisulfite-seq] |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
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| Summary |
DNA methylation and histone lysine tri-methylation at H3K27 (H3K27me3) are the two primary epigenetic marks for transcriptional silencing essential for cell fate determination and cell lineage commitment during development1, 2. These two marks are mutually exclusive and target distinct sets of genes in the mammalian genome3. However, whether and how H3K27me3 shapes the DNA methylome remains unknown. Here, we report that the loss of H3K27me3 modification leads to increased DNA methylation at previously marked H3K27me3 sites, revealing that H3K27me3 negatively regulates DNA methylation. Genome-wide analysis of H3 ubiquitination, essential for recruitment and activation of DNA methyltransferase DNMT14, reveals the absence of H3 ubiquitination at H3K27me3 marked nucleosomes. Moreover, loss of H3K27me3 modification induces an increase in H3K18 ubiquitination at the corresponding hypermethylated loci. Importantly, we show that H3K27me3 directly inhibits UHRF1-mediated H3 ubiquitination toward nucleosomes in a defined biochemical assay. Furthermore, UHRF1 is required for the increase in DNA methylation at previously marked H3K27me3 sites in cells with abolished H3K27me3 modification. Taken together, our findings reveal a general mechanism for H3K27me3-mediated shaping of the mammalian DNA methylome via modulation of H3 ubiquitination.
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| Overall design |
We performed WGBS (whole genome bisulfite sequencing) in WT HeLa cell, SUZ12 KO HeLa cell (two replications), WT E14 cell, Suz12 KO E14 cell, Uhrf1 KO E14 cell, Suz12/Uhrf1 double KO E14 cell. We mapped H3K27me3 ChIP-seq and H3K27me3 ChIP-BS-seq(chromatin immunoprecipitation bisulfite sequencing) in WT HeLa cell. We did RNA-seq in WT and SUZ12 KO HeLa cell (two replications). H3K18ub ChIP-seq in WT HeLa cell, SUZ12 KO HeLa cell, WT E14 cell and Uhrf1 KO E14 cell were also performed.
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| Contributor(s) |
Zhang H, Liu Y, Zhu Y, Xie Y, Liu J, Lu F |
| Citation missing |
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| Submission date |
Oct 05, 2020 |
| Last update date |
Jul 01, 2022 |
| Contact name |
Falong Lu |
| E-mail(s) |
fllu@genetics.ac.cn
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| Phone |
+861064803741
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| Organization name |
Institute of Genetics and Developmental Biology
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| Street address |
1 West Beichen Road Chaoyang District
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| City |
Beijing |
| State/province |
- |
| ZIP/Postal code |
100101 |
| Country |
China |
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| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE159043 |
H3K27me3 shapes DNA methylome by inhibiting UHRF1-mediated H3 ubiquitination |
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| Relations |
| BioProject |
PRJNA667470 |
| SRA |
SRP286409 |
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