This SuperSeries is composed of the SubSeries listed below.
Jarid1b targets genes regulating development and is involved in neural differentiation.
Specimen part
View SamplesThe Polycomb group (PcG) proteins form chromatin-modifying complexes that are essential for embryonic development and stem cell renewal and are commonly deregulated in cancer. Here, we identify their target genes using genome-wide location analysis in human embryonic fibroblasts. We find that Polycomb-Repressive Complex 1 (PRC1), PRC2, and tri-methylated histone H3K27 co-occupy >1000 silenced genes with a strong functional bias for embryonic development and cell fate decisions. We functionally identify 40 genes derepressed in human embryonic fibroblasts depleted of the PRC2 components (EZH2, EED, SUZ12) and the PRC1 component, BMI-1. Interestingly, several markers of osteogenesis, adipogenesis, and chrondrogenesis are among these genes, consistent with the mesenchymal origin of fibroblasts. Using a neuronal model of differentiation, we delineate two different mechanisms for regulating PcG target genes. For genes activated during differentiation, PcGs are displaced. However, for genes repressed during differentiation, we paradoxically find that they are already bound by the PcGs in nondifferentiated cells despite being actively transcribed. Our results are consistent with the hypothesis that PcGs are part of a preprogrammed memory system established during embryogenesis marking certain key genes for repressive signals during subsequent developmental and differentiation processes.
Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions.
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View SamplesThe H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) is dispensable for embryonic stem cell (ESC) self-renewal, but essential for ESC differentiation along the neural lineage. During neural differentiation, Jarid1b depleted ESCs fail to efficiently silence lineage-inappropriate genes, specifically stem and germ cell genes. Our results delineate an essential role for Jarid1b-mediated transcriptional control during ESC differentiation.
Jarid1b targets genes regulating development and is involved in neural differentiation.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
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View SamplesEmbryonic development is tightly regulated by transcription factors and chromatin-associated proteins. H3K4me3 is associated with active transcription and H3K27me3 with gene repression, while the combination of both keeps genes required for development in a plastic state. Here we show that deletion of the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) results in major neonatal lethality due to respiratory failure. Jarid1b knockout embryos have several neural defects including disorganized cranial nerves, defects in eye development and increased incidences of exencephaly. Moreover, in line with an overlap of Jarid1b and Polycomb targets genes, Jarid1b knockout embryos display homeotic skeletal transformations typical for Polycomb mutants. Genome-wide analysis demonstrated that normally inactive genes encoding developmental regulators acquire aberrant H3K4me3 in early Jarid1b knockout embryos. H3K4me3 accumulates as embryonic development proceeds, leading to increased expression of neural master regulators in knockouts. Taken together, these results suggest that Jarid1b contributes to mouse development by protecting developmental genes from inappropriate acquisition of active histone modifications.
The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3.
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View SamplesWe used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes in fbn5-1 T-DNA insertion Arabidopsis mutant.
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View SamplesThe goal of this study is to identify deferentially expressed genes among three groups of individuals of the same family. These groups are : affected, unaffected wild, unaffected carrier.
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View SamplesThe scientific rationale for the clinical advancement of Lm-based immunotherapies is in part due to hallmark observations in the mouse infection model where a single immunization with sublethal doses of WT Lm confers lifelong protection against lethal WT Lm challenge. Protection is entirely dependent upon potent bacterial-specific CD4+ and CD8+ T cell immunity. While our previous investigations have demonstrated the antitumor potency of therapeutic immunization with LADD-Ag , here we describe for the first time, the immunologic correlates of this antitumor efficacy.
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Sex, Specimen part, Disease, Cell line
View SamplesGrain yield and protein content were determined for six wheat cultivars grown over three years at multiple sites and at multiple N-fertilizer inputs. Although grain protein was negatively correlated with yield, some grain samples had higher protein contents than expected based on their yields, a trait referred to as grain protein deviation (GPD). We used novel statistical approaches to calculate GPD across environment and to correlate gene expression in the developing caryopsis with this trait. The yield and protein content were initially adjusted for nitrogen fertilizer inputs, and then adjusted for yield (to remove the negative correlation) resulting in environmental corrected GPD. The transcriptome data for all samples were subjected to Principal Component Analysis (PCA) and ANOVA to identify individual Principal Components (PCs) correlating with GPD alone. Scores of the selected PCs significantly related to cultivar differences and GPD but not to the yield or protein content were identified as reflecting a multivariate pattern of gene expression related to genetic variation in GPD. Sets of genes significant for these PCs and hence GPD were identified as candidate genes determining cultivar differences in GPD.
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Specimen part
View SamplesAn important but largely unmet challenge in understanding the mechanisms that govern formation of specific organs is to decipher the complex and dynamic genetic programs exhibited by the diversity of cell types within the tissue of interest. Here, we use an integrated genetic, genomic and computational strategy to comprehensively determine the molecular identities of distinct myoblast subpopulations within the Drosophila embryonic mesoderm at the time that cell fates are initially specified. A compendium of gene expression profiles was generated for primary mesodermal cells purified by flow cytometry from appropriately staged wild-type embryos and from twelve genotypes in which myogenesis was selectively and predictably perturbed. A statistical meta-analysis of these pooled datasetsbased on expected trends in gene expression and on the relative contribution of each genotype to the detection of known muscle genesprovisionally assigned hundreds of differentially expressed genes to particular myoblast subtypes. Whole embryo in situ hybridizations were then used to validate the majority of these predictions, thereby enabling true positive detection rates to be estimated for the microarray data. This combined analysis reveals that myoblasts exhibit much greater gene expression heterogeneity and overall complexity than was previously appreciated. Moreover, it implicates the involvement of large numbers of uncharacterized, differentially expressed genes in myogenic specification and subsequent morphogenesis. These findings also underscore a requirement for considerable regulatory specificity for generating diverse myoblast identities. Finally, to illustrate how the developmental functions of newly identified myoblast genes can be efficiently surveyed, a rapid RNA interference assay that can be scored in living embryos was developed and applied to selected genes. This integrated strategy for examining embryonic gene expression and function provides a substantially expanded framework for further studies of this model developmental system.
An integrated strategy for analyzing the unique developmental programs of different myoblast subtypes.
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