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| Status |
Public on Jul 26, 2018 |
| Title |
Mtf2-PRC2 control of canonical Wnt signaling is required for definitive erythropoiesis [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Polycomb repressive complex 2 (PRC2) accessory proteins play substoichiometric, tissue-specific roles to recruit PRC2 to specific genomic loci or increase enzymatic activity, while PRC2 core proteins are required for complex stability and global levels of trimethylation of histone 3 at lysine 27 (H3K27me3). Here, we demonstrate a role for the classical PRC2 accessory protein Mtf2/Pcl2 in the hematopoietic system that is more akin to that of a core PRC2 protein. Mtf2-/- erythroid progenitors demonstrate markedly decreased core PRC2 protein levels and a global loss of H3K27me3 at promoter-proximal regions. The resulting de-repression of transcriptional and signaling networks blocks definitive erythroid development, culminating in Mtf2-/- embryos dying by e15.5 due to severe anemia. Gene regulatory network (GRN) analysis demonstrated Mtf2 directly regulates Wnt signaling in erythroblasts, leading to activated canonical Wnt signaling in Mtf2-deficient erythroblasts, while chemical inhibition of canonical Wnt signaling rescued Mtf2-deficient erythroblast differentiation in vitro. Using a combination of in vitro, in vivo and systems analyses, we demonstrate that Mtf2 is a critical epigenetic regulator of Wnt signaling during erythropoiesis and recast the role of polycomb accessory proteins in a tissue-specific context.
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| Overall design |
CD71+Ter119-/lo and CD71+Ter119high cell fractions from fetal livers of e14.5 WT and Pcl2-/- embryos were FACS-sorted and RNA was isolated isolated. RNAseq was performed to determine gene expression. (560Iplus the WT sample, 548Bminus is the Pcl2-/- sample)
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| Contributor(s) |
Stanford WL, Rothberg JL |
| Citation(s) |
29736258 |
| Submission date |
Aug 24, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
William Stanford |
| E-mail(s) |
wstanford@ohri.ca
|
| Phone |
613-737-8899
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| Organization name |
Ottawa Hospital Research Institute
|
| Lab |
Stanford
|
| Street address |
501 Smyth Road
|
| City |
Ottawa |
| State/province |
Ontario |
| ZIP/Postal code |
K1H 8L6 |
| Country |
Canada |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE72288 |
Mtf2-PRC2 control of canonical Wnt signaling is required for definitive erythropoiesis |
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| Relations |
| BioProject |
PRJNA293666 |
| SRA |
SRP062762 |
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