RNA-binding proteins (RBPs) are critical regulators of gene expression and elucidating the interactions of RBPs with their RNA targets is necessary to understand how combinations of RBPs control transcriptome expression. The Quaking-related (QR) sub-family of STAR domain RBPs includes developmental regulators and tumor suppressors such as C. elegans GLD-1, which functions as a master regulator of germ line development. To understand how GLD-1 interacts with the transcriptome, we identified GLD-1 associated mRNAs by a ribonomic approach. The scale of GLD-1 mRNA interactions allowed us to determine rules governing GLD-1 target selection and to derive a predictive model where GLD-1 association with mRNA is based on the number and strength of 7-mer GLD-1 binding elements (GBEs) within UTRs. GLD-1/mRNA interactions were quantified, and predictions were verified both in vitro and in live animals, including by transplantation experiments where weak and strong GBEs imposed translational repression of increasing strength on a non-target mRNA.Importantly, this study provides a unique quantitative picture of how an RBP interacts with its mRNA targets. As combinatorial regulation by multiple RBPs is thought to regulate gene expression, quantification of RBP/mRNA interactions should be a way to predict and potentially modify biological outcomes of complex posttranscriptional regulatory networks, and our analysis suggests that such an approach is possible.
A quantitative RNA code for mRNA target selection by the germline fate determinant GLD-1.
Specimen part
View SamplesLong-term treatment of Kasumi-1 cells at clinically attained doses of dasatinib led to decreased drug-sensitivity by means of IC50 values (relative to treatment-naive cells). Changes were paralled by profound alterations in c-KIT expression and cell signaling signatures. Upon brief discontinuation of dasatinib treatment, these alterations reversed and drug sensitivity was restored.
Transitory dasatinib-resistant states in KIT(mut) t(8;21) acute myeloid leukemia cells correlate with altered KIT expression.
Cell line
View SamplesRat kidney in normo- and hypotensive animals.
A physiogenomic approach to study the regulation of blood pressure.
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View SamplesCombinatorial control of gene expression by the three yeast repressors Mig1, Mig2 and Mig3
Combinatorial control of gene expression by the three yeast repressors Mig1, Mig2 and Mig3.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
The BEN domain is a novel sequence-specific DNA-binding domain conserved in neural transcriptional repressors.
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View SamplesAffymetrix arrays measuring gene expression in 3 Drosophila Insensitive mutant embryos and 3 Drosophila wt mutant embryos
The BEN domain is a novel sequence-specific DNA-binding domain conserved in neural transcriptional repressors.
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View SamplesThe response to nitrogen starvation was studied in S. pombe. This experiment contains expression data from Affymetrix Yeast 2.0 arrays.
Nitrogen depletion in the fission yeast Schizosaccharomyces pombe causes nucleosome loss in both promoters and coding regions of activated genes.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition.
Specimen part, Cell line
View SamplesIntra-tumor heterogeneity is a hallmark of glioblastoma multiforme, and thought to negatively affect treatment efficacy. Here we establish libraries of glioma-initiating cell (GIC) clones from patient samples and find extensive molecular and phenotypic variability between clones, including a wide range of responses to radiation and drugs. This widespread variability was observed as a continuum of multitherapy resistance phenotypes linked to a proneural-to-mesenchymal shift in the transcriptome.
Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition.
Specimen part, Cell line
View SamplesGrainy head (Grh) is a conserved transcription factor (TF) controlling epithelial differentiation and regeneration. To elucidate Grh functions, we identified embryonic Grh targets by ChIP-seq and gene expression analysis. We show that Grh controls hundreds of target genes. Repression or activation correlates with the distance of Grh binding sites to the transcription start sites of its targets. Analysis of 54 Grh-responsive enhancers during development and upon wounding suggests cooperation with distinct TFs in different contexts. In the airways, Grh repressed genes encode key TFs involved in branching and cell differentiation. Reduction of the POU-domain TF, Vvl, (ventral veins lacking) largely ameliorates the airway morphogenesis defects of grh mutants. Vvl and Grh proteins additionally interact with each other and regulate a set of common enhancers during epithelial morphogenesis. We conclude that Grh and Vvl participate in a regulatory network controlling epithelial maturation.
Genome-wide identification of Grainy head targets in <i>Drosophila</i> reveals regulatory interactions with the POU domain transcription factor Vvl.
No sample metadata fields
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