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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 05, 2017 |
| Title |
Genome-wide H2B monoubiquitination regulates gene expression by coordinating H3K4me3 and H3K27me3 [RNA-Seq Data Set] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| 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.
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| Overall design |
mRNA profiles of Rnf40+/+ and Rnf40-/- mouse embroynic fibroblasts were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000
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| Contributor(s) |
Xie W, Johnsen SA |
| Citation(s) |
28209164 |
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| Submission date |
Aug 20, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Steven A Johnsen |
| E-mail(s) |
steven.johnsen@med.uni-goettingen.de
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| Organization name |
University Medical Center Göttingen
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| Department |
Clinic for General, Visceral and Pediatric Surgery
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| Lab |
AG Tumorepigenetics
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| Street address |
Robert Koch Strasse 40
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| City |
Göttingen, Niedersachsen |
| State/province |
Niedersachsen |
| ZIP/Postal code |
37075 |
| Country |
Germany |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE72239 |
Genome-wide H2B monoubiquitination regulates gene expression by coordinating H3K4me3 and H3K27me3 |
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| Relations |
| BioProject |
PRJNA293454 |
| SRA |
SRP062675 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE72238_RNF40_WT_KO.txt.gz |
639.7 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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