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Series GSE159042 Query DataSets for GSE159042
Status Public on Jun 27, 2022
Title H3K27me3 shapes DNA methylome by inhibiting UHRF1-mediated H3 ubiquitination [ChIP-seq]
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
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.
 
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.
 
Contributor(s) Zhang H, Liu Y, Zhu Y, Xie Y, Liu J, Lu F
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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
Phone +861064803741
Organization name Institute of Genetics and Developmental Biology
Street address 1 West Beichen Road Chaoyang District
City Beijing
State/province -
ZIP/Postal code 100101
Country China
 
Platforms (2)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (11)
GSM4818077 E14_WT_H3K18ub_ChIP_seq
GSM4818078 E14_Uhrf1_KO_H3K18ub_ChIP_seq
GSM4818079 E14_WT_input_ChIP_seq
This SubSeries is part of SuperSeries:
GSE159043 H3K27me3 shapes DNA methylome by inhibiting UHRF1-mediated H3 ubiquitination
Relations
BioProject PRJNA667469
SRA SRP286411

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Supplementary file Size Download File type/resource
GSE159042_RAW.tar 2.0 Gb (http)(custom) TAR (of BED, BROADPEAK, BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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