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| Status |
Public on Jan 21, 2016 |
| Title |
H2A.Z.1 mono-ubiquitylation antagonizes BRD2 to maintain poised chromatin in ESCs [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Histone variant H2A.Z occupies the promoters of active and poised, bivalent genes in ESCs to regulate developmental programs, yet how it contributes to these contrasting states is poorly understood. Here, we investigate the function of H2A.Z.1 mono-ubiquitylation (H2A.Z.1ub) by mutation of the PRC1 target residues (H2A.Z.1K3R3). We show that H2A.Z.1K3R3 is properly incorporated at target promoters in murine ESCs (mESCs), however, loss of mono-ubiquitylation leads to de-repression of bivalent genes, loss of Polycomb binding, and to faulty lineage commitment. Using quantitative proteomics, we find that tandem bromodomain proteins, including the BET family member Brd2, are enriched in H2A.Z.1 chromatin. We further show that Brd2 is gained at de-repressed promoters in H2A.Z.1K3R3 mESCs whereas Brd2 inhibition restores gene silencing at these sites. Together, our study reveals an antagonistic relationship between H2A.Z.1ub and Brd2 to regulate the transcriptional balance at bivalent genes to enable proper execution of developmental programs.
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| Overall design |
RNA-Seq analysis on mouse embryonic stem cells harboring H2A.Z or H2A.Z.K3R3 (3 C-terminal lysines mutated to arginines) tagged with YFP, in the presence of a knockdown hairpin targeting the endogenous H2A.Z transcript.
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| Contributor(s) |
Surface LE, Fields PA, Boyer LA |
| Citation(s) |
26804911 |
| |
| Submission date |
Dec 11, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Laurie A Boyer |
| E-mail(s) |
lboyer@mit.edu
|
| Phone |
617 324-3335
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| Organization name |
Massachusetts Institute of Technology
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| Department |
Biology
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| Lab |
Boyer
|
| Street address |
77 Massachusetts Avenue
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02139 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE53208 |
H2A.Z.1 mono-ubiquitylation antagonizes BRD2 to maintain poised chromatin in ESCs |
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| Relations |
| BioProject |
PRJNA231112 |
| SRA |
SRP033699 |
