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Series GSE72237 Query DataSets for GSE72237
Status Public on Jan 05, 2017
Title Genome-wide H2B monoubiquitination regulates gene expression by coordinating H3K4me3 and H3K27me3 [ChIP-Seq Data Set]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Gene body-associated monoubiquitination of H2B (H2Bub1) coupled with promoter-associated active histone modifications such as trimethylation H3 on lysine 4 (H3K4me3) and acetylation H3 on lysine 27 (H3K27ac) facilitate gene transcription. However, surprisingly, only a subset of genes is altered in their expression following knockdown of H2B ubiquitin-protein ligases RNF20 or RNF40 in human cells. In order to obtain a more complete genome- and transcriptome-wide understanding of the role of H2Bub1 in gene transcription, we generated tamoxifen-inducible Rnf40 knockout mouse embryonic fibroblasts (MEFs). Mapping of H2Bub1, H3K4me3, H3K27me3, and H3K27ac occupancy identified an “ascending” gene cluster including bivalent genes, which is occupied by low to moderate amounts of H2Bub1 and exhibits high variability in transcription. We provide evidence that the variation in expression is highly associated with the variations in H3K4me3, H3K27me3, and H3K27ac occupancy. Moreover, these variably marked “ascent” genes are selectively regulated in Rnf40-deficient MEFs. Consistent with previous studies, the effect of Rnf40 loss on the expression of genes within this cluster is also variable with some genes demonstrating increased while others decreased mRNA levels following Rnf40 deletion. Importantly, we identified the Ezh2 gene as an Rnf40/H2Bub1 target whose expression significantly decreased in Rnf40-deficient MEFs. Notably, we show that genes upregulated following Rnf40 deletion are enriched for H3K27me3, which is decreased following Rnf40 deletion, and these effects can be mimicked by treating with a small molecule EZH2 inhibitor. On the other hand, consistent with findings in many eukaryotic systems, genes whose expression decreases following Rnf40 deletion show an enrichment of H3K4me3 and decreased levels following deletion. Together, we provide mechanistic information by which Rnf40, presumably via H2Bub1, modulates gene expression via coordination of the active and repressive marks H3K4me3 and H3K27me3.
Overall design examination of H2Bub1, H3K4me3, H3K27me3, and H3K27ac in Rnf40+/+ and Rnf40-/- mouse embryonic fibroblasts were generated by deep sequencing
Contributor(s) Xie W, Johnsen SA
Citation(s) 28209164
Submission date Aug 20, 2015
Last update date May 15, 2019
Contact name Steven A Johnsen
Organization name University Medical Center Göttingen
Department Clinic for General, Visceral and Pediatric Surgery
Lab AG Tumorepigenetics
Street address Robert Koch Strasse 40
City Göttingen, Niedersachsen
State/province Niedersachsen
ZIP/Postal code 37075
Country Germany
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (19)
GSM1858312 H2Bub1_WT_rep1
GSM1858313 H2Bub1_WT_rep2
GSM1858314 H3K4me3_WT_rep1
This SubSeries is part of SuperSeries:
GSE72239 Genome-wide H2B monoubiquitination regulates gene expression by coordinating H3K4me3 and H3K27me3
BioProject PRJNA293455
SRA SRP062674

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SOFT formatted family file(s) SOFTHelp
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Supplementary file Size Download File type/resource
GSE72237_H2Bub1_WT.bigwig 95.8 Mb (ftp)(http) BIGWIG
GSE72237_H3K27ac_KO.bigwig 95.5 Mb (ftp)(http) BIGWIG
GSE72237_H3K27ac_WT.bigwig 93.5 Mb (ftp)(http) BIGWIG
GSE72237_H3K27me3_KO.bigwig 147.3 Mb (ftp)(http) BIGWIG
GSE72237_H3K27me3_WT.bigwig 161.1 Mb (ftp)(http) BIGWIG
GSE72237_H3K4me3_KO.bigwig 220.3 Mb (ftp)(http) BIGWIG
GSE72237_H3K4me3_WT.bigwig 200.1 Mb (ftp)(http) BIGWIG
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Raw data are available in SRA
Processed data are available on Series record

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