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Series GSE72286 Query DataSets for GSE72286
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
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.
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)
Contributor(s) Stanford WL, Rothberg JL
Citation(s) 29736258
Submission date Aug 24, 2015
Last update date May 15, 2019
Contact name William Stanford
Phone 613-737-8899
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
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (4)
GSM1859517 548Bminus-Ter119minus
GSM1859518 548Bminus-Ter119plus
GSM1859519 560Iplus-Ter119minus
This SubSeries is part of SuperSeries:
GSE72288 Mtf2-PRC2 control of canonical Wnt signaling is required for definitive erythropoiesis
BioProject PRJNA293666
SRA SRP062762

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Supplementary file Size Download File type/resource
GSE72286_548B_Ter119+-gene_exp.diff.gz 1.3 Mb (ftp)(http) DIFF
GSE72286_560I548B_Ter119+gene_exp.diff.gz 1.3 Mb (ftp)(http) DIFF
GSE72286_560I548B_Ter119-gene_exp.diff.gz 1.3 Mb (ftp)(http) DIFF
GSE72286_560I_Ter119+-gene_exp.diff.gz 1.3 Mb (ftp)(http) DIFF
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