This SuperSeries is composed of the SubSeries listed below.
<i>miR-9a</i> mediates the role of Lethal giant larvae as an epithelial growth inhibitor in <i>Drosophila</i>.
Age, Specimen part
View SamplesAffymetrix microarray to detect changes in gene expression between lgl27S3/lglE2S31 and FRT82B larvae
<i>miR-9a</i> mediates the role of Lethal giant larvae as an epithelial growth inhibitor in <i>Drosophila</i>.
Age, Specimen part
View SamplesPost-transcriptional regulation of mRNA by the RNA binding protein HuR is required in B cells for the germinal centre reaction and for the production of class-switched antibodies in response to T-independent antigens. Transcriptome-wide examination of RNA isoforms, abundance and translation in HuR-deficient B cells, together with direct measurements of HuR-RNA interaction, revealed that HuR-dependent mRNA splicing affects hundreds of transcripts including the dihydrolipoyl succinyltransferase (Dlst), a subunit of the aketoglutaratedehydrogenase (aKGDH) enzyme. In the absence of HuR, defective mitochondrial metabolism results in high levels of reactive oxygen species and B cell death. Our study shows how post-transcriptional processes control the balance of energy metabolism required for B cell proliferation and differentiation. Overall design: Sequencing analysis of B cell transcriptome using Illumina TruSeq mRNA sample prep kit and Illumina platform. RNA was isolated from ex-vivo or LPS-activated (48h) splenic B cells from HuRflox/flox x mb1wt control or HuRflox/flox x mb1cre mice. 3-4 biological replicates per genotype and condition.
The RNA-binding protein HuR is essential for the B cell antibody response.
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View SamplesMAPK scaffolds, such as IQGAP1, assemble pathway kinases together to effect signal transmission and disrupting scaffold function therefore offers a potentially orthogonal approach to MAPK cascade inhibition. Consistent with this possibility, we observed an IQGAP1 requirement in Ras-driven tumorigenesis in mouse and human tissue. Delivery of the IQGAP1 WW peptide sequence that mediates Erk1/4 binding, moreover, disrupted IQGAP1-Erk1/2 interactions, abolished Ras/Raf-driven tumorigenesis, bypassed acquired resistance to the B-Raf inhibitor vemurafinib (PLX- 4032), and acts as a systemically deliverable therapeutic to significantly increase lifespan of tumor bearing mice. Scaffold-kinase interaction blockade (SKIB) acts by a mechanism distinct from direct kinase inhibition and represents a strategy to target over-active oncogenic kinase cascades in cancer.
IQGAP1 scaffold-kinase interaction blockade selectively targets RAS-MAP kinase-driven tumors.
Time
View SamplesDisrupted differentiation is a hallmark of numerous diseases, which in epidermis alone impact >25% of the population. In a search for dominant mediators of differentiation, we defined a requirement for the ZNF750 nuclear protein in terminal epidermal differentiation. ZNF750 controlled genes mutated in numerous human skin diseases, including FLG, LOR, LCE3B, ALOXE3, and SPINK5. ZNF750 potently induced progenitor differentiation via an evolutionarily conserved C2H2 zinc finger motif. The epidermal master regulator, p63, bound the ZNF750 promoter and was necessary for its induction. ZNF750 restored differentiation to p63-deficient tissue, suggesting it acts downstream of p63. A search for functionally important ZNF750 targets via analysis of ZNF750-regulated genes identified KLF4, a transcription factor that activates late epidermal differentiation genes. ZNF750 binds the Klf4 promoter and controls its expression. ZNF750 thus provides a direct link between a tissue-specifying factor, p63, and an effector of terminal differentiation, Klf4, and represents a potential future target for disorders of this process.
ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation.
Specimen part, Treatment
View SamplesThe transcriptional basis for disrupted epidermal differentiation arising from TP63 AEC mutations remains to be elucidated. Here we present an organotypic model of AEC dysfunction that phenocopies differentiation defects observed in AEC patient skin. Transcriptional analysis of model AEC tissue revealed impaired induction of differentiation regulators, including OVOL1, GRHL3, KLF4, PRDM1 and ZNF750. Genome wide binding analyses of TP63 during epidermal differentiation showed direct binding of OVOL1, GRHL3, and ZNF750 promoters suggesting AEC mutants prevent normal activation of these targets by direct transcriptional interference. Remarkably, exogenous ZNF750 restores impaired epidermal differentiation caused by AEC mutation. Thus, repression of ZNF750 is central to disrupted epidermal differentiation in model AEC tissue.
Genomic profiling of a human organotypic model of AEC syndrome reveals ZNF750 as an essential downstream target of mutant TP63.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
CSNK1a1 Regulates PRMT1 to Maintain the Progenitor State in Self-Renewing Somatic Tissue.
Specimen part, Treatment
View SamplesHere we determine the target gene sets controlled by PRMT1 or CSNK1a1 in maintaining the undifferentiated state of primary human keratinocytes.
CSNK1a1 Regulates PRMT1 to Maintain the Progenitor State in Self-Renewing Somatic Tissue.
Treatment
View SamplesGoal was to identify yeast genes whose expression changed as a function of the shift from growth in bulk culture to growth in an air-liquid interfacial biofilm.
Ethanol-independent biofilm formation by a flor wine yeast strain of Saccharomyces cerevisiae.
Specimen part
View SamplesComparison of gene expression profiles from C. elegans wildtype strain (N2) treated with L4440 and T25B9.1 RNAi for 5 days after L4 larvae stage. Jena Centre for Systems Biology of Ageing - JenAge (ww.jenage.de) Overall design: 6 samples in 2 groups: N2, L4440 5 days (3 Samples); N2, T25B9.1 5 days (3 Samples)
Impairing L-Threonine Catabolism Promotes Healthspan through Methylglyoxal-Mediated Proteohormesis.
Sex, Age, Specimen part, Cell line, Subject
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