PRC2 Promotes Canalisation During Endodermal Differentiation
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ABSTRACT:
PROVIDER: PRJNA1208096 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:PRC2 Promotes Canalisation During Endodermal Differentiation [microarray]
| PRJNA1207681 | ENA
Project description:PRC2 Promotes Canalisation During Endodermal Differentiation [ChIP-Seq]
| PRJNA1208099 | ENA
Project description:PRC2 Promotes Canalisation During Endodermal Differentiation [4sU-seq]
| PRJNA1208097 | ENA
Project description:In this study we employed a mouse embryonic stem cell in vitro system to differentiate ESCs into Anterior Definitive Endoderm (ADE) to model primitive streak formation and early gastrulation. To establish the gene expression changes which occurred during this differentiation we performed whole genome expression analysis on RNA isolated from FACS purified cell populations. We utilised a dual reporter mESC line (B6), bearing fluorescent reporters knocked in to the Gsc (GFP) and Hhex (Redstar) loci. GSC is a marker of the PS/mesendoderm and HHEX marks definitive endoderm lineages and expression of these reporters allowed us to isolate developmentally distinct populations during the differentiation. Using the expression profile of the untreated differentiation as a reference, we investigated the developmental impact of impaired H3K27me3 deposition on ADE differentiation by inhibiting EZH2, the core catalytic component of polycomb repressive complex 2 (PRC2) using the small molecule inhibitor EPZ6438. We found that ADE differentiation recapitulated the in vivo developmental tradjectory and that PRC2 inhibition enhanced endodermal differentiation efficiency, but did so at the cost of lineage fidelity.
2025-01-13 | GSE286087 | GEO
Project description:ChIP-seq was performed to determine the transcriptional activity of genes during endodermal differentiation RNA pol II occupancy and histone marks of elongation and gene repression were analyzed during early endodermal differentiation
2012-09-25 | E-GEOD-41111 | biostudies-arrayexpress
Project description:ChIP-seq was performed to determine the transcriptional activity of genes during endodermal differentiation
2012-09-25 | GSE41111 | GEO
Project description:In this study we employed a mouse embryonic stem cell (ESCs) differentiation system to convert pluripotent ESCs into Anterior Definitive Endoderm (ADE) to model primitive streak formation and early gastrulation. To monitor the progression of the differentiation we utilised a dual reporter mESC line (B6) bearing fluorescent reporters knocked in to the Gsc (marker of the PS/mesendoderm tagged with GFP) and Hhex (marker of definitive endoderm lineages tagged with Redstar) loci. To establish the transcriptional changes which occurred during a phase of differentiation that resembles the epithelial to mesenchymal transition (EMT) at the primitive streak (PS), we performed 4sU-seq analysis on FACS sorted GSC negative and positive populations from day 3 and day 4 of differentiation. Using this approach, in combination with genome-wide gene expression analysis and ChIP-seq data, we: i). Found that changes in the gene expression where primarily regulated at the levels of transcription; ii). Identified putative enhancer elements with bi-directional transcription signatures proximal to developmentally regulated genes; iii). Determined that transcriptional upregulation of genes did not require the prior loss of H3K27me3 at gene TSSs.
2025-01-13 | GSE286193 | GEO
Project description:In this study we employed a mouse embryonic stem cell (ESCs) differentiation system to convert pluripotent ESCs into Anterior Definitive Endoderm (ADE) to model primitive streak formation and early gastrulation. To monitor the progression of the differentiation we utilised a dual reporter mESC line (B6) bearing fluorescent reporters knocked in to the Gsc (marker of the PS/mesendoderm tagged with GFP) and Hhex (marker of definitive endoderm lineages tagged with Redstar) loci. To monitor changes in the chromatin landscape during this differentiation we performed ChIP-seq for H3K27me3 and H3K4me3 (modifications associated with gene repression and activation respectively) in each of nine FACs sorted ADE populations. Using this approach, in combination with genome-wide gene expression analysis, we; i). Found that changes in gene expression/transcription were both predictive of and predicted by dynamic changes in the levels of these histone modifications at gene promoters; ii). Found that changes in H3K27me3 levels at TSS are more dynamic than the levels of H3K4me3; iii). Determined that transcriptional upregulation of genes did not require the prior loss of H3K27me3 at gene TSSs.
2025-01-13 | GSE286192 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-01-13 | GSE286195 | GEO
Project description:Polycomb Repressive Complex 2 (PRC2) catalyzes histone H3 lysine 27 tri-methylation, an epigenetic modification associated with gene repression. H3K27me3 is enriched at the promoters of a large cohort of developmental genes in embryonic stem cells (ESCs). Loss of H3K27me3 leads to a failure of ESCs to properly differentiate, which presents a major roadblock for dissecting the precise roles of PRC2 activity during lineage commitment. While recent studies suggest that loss of H3K27me3 leads to changes in DNA methylation in ESCs, how these two pathways coordinate to regulate gene expression programs during lineage commitment is poorly understood. Here, we analyzed gene expression and DNA methylation levels in several PRC2 mutant ESC lines that maintain varying levels of H3K27me3. We found that maintenance of intermediate levels of H3K27me3 allowed for proper temporal activation of lineage genes during directed differentiation of ESCs to spinal motor neurons (SMNs). However, genes that function to specify other lineages failed to be repressed, suggesting that PRC2 activity is necessary for lineage fidelity. We also found that H3K27me3 is antagonistic to DNA methylation in cis. Furthermore, loss of H3K27me3 leads to a gain in promoter DNA methylation in developmental genes in ESCs and in lineage genes during differentiation. Thus, our data suggest a role for PRC2 in coordinating dynamic gene repression while protecting against inappropriate promoter DNA methylation during differentiation. Embryonic Stem Cell (ESC) lines mutant for PRC2 core components Suz12 (Suz12GT and Suz12delta) and Eed (Eednull) were subjected to in vitro directed differentiation down the spinal motor neuron lineage. ESCs and day 5 differentiated cells from the three mutant lines and wild-type were used for Reduced Representation Bisulfite Sequencing (RRBS).
2014-11-17 | E-GEOD-53507 | biostudies-arrayexpress