Transcription is a major contributor to genome instability. A main cause of transcription-associated instability relies on the capacity of transcription to stall replication. Such genome instability is increased in RNAPII mutants.
RNA polymerase II contributes to preventing transcription-mediated replication fork stalls.
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View SamplesOur analysis indicates that at least 37% of the transcriptome mobilized by KNAT1 is potentially dependent on this interaction, and includes genes involved in secondary cell wall modifications and phenylpropanoid biosynthesis. Overall design: Seven-day-old Arabidopsis wild-type (No-0) and 35S::KNAT1 seedlings growing in MS plates under continuous light were transferred to a liquid growing medium supplemented with 10 µM paclobutrazol (PAC) for 18 h. Seedlings were then incubated with 10 µM PAC+100 µM GA3 or maintained in 10 µM PAC for 5 h.
Regulation of xylem fiber differentiation by gibberellins through DELLA-KNAT1 interaction.
Specimen part, Treatment, Subject
View SamplesTissue-specific differentiation and inflammatory programmes are thought to independently contribute to disease. The orphan nuclear receptor NR5A2 is a key regulator of pancreas differentiation, and SNPs in and near the human gene are associated with risk of pancreatic cancer. In mice, Nr5a2 heterozygosity sensitizes the pancreas to damage, impairs regeneration, and cooperates with mutant Kras in tumor progression. Through transcriptomic analysis, we uncovered a basal pre-inflammatory state in the pancreas of heterozygous mice that is reminiscent of pancreatitis-induced inflammation and is conserved in histologically normal human pancreata with reduced Nr5a2 mRNA expression. In mice, Nr5a2 undergoes a dramatic transcriptional switch from tissue-specific to inflammatory loci, which promotes AP-1-dependent inflammatory gene transcription. Deletion of c-Jun in the pancreas of Nr5a2+/- mice rescues the pre-inflammatory phenotype and the defective regenerative response to damage. These findings provide compelling evidence that the same transcriptional networks supporting homeostasis in normal tissue can be subverted to foster inflammation upon genetic or environmental constraints. Overall design: A mild acute pancreatitis was induced by seven hourly injections of the CCK analog caerulein (Bachem) at 50 ug/kg. Briefly, animals were weighted before the beginning of the procedure and caerulein was administered i.p. Mice were sacrificed by cervical dislocation 8h, 24h,and 48h after the first injection. Three animals of each genotype and timepoint were analysed.
Transcriptional regulation by NR5A2 links differentiation and inflammation in the pancreas.
Specimen part, Treatment, Subject
View SamplesTo inhibit INS expression, we used shRNA to target the INS promoter. We find that knocking down INS expression with such an shRNA targeting the INS promoter significantly affects expression of 259 genes. Overall design: mRNA profiles of EndoC ßH1 with or without shRNA targetting INS promoter were generated by deep sequencing, in triplicate, using Illumina Hiseq 2500.
<i>Insulin</i> promoter in human pancreatic β cells contacts diabetes susceptibility loci and regulates genes affecting insulin metabolism.
Specimen part, Cell line, Treatment, Subject
View SamplesGenetically engineered mouse models of cancer represent valuable biological tools that can be used to filter genome-wide expression datasets generated from human prostate tumours, and identify gene expression alterations that are functionally important to cancer development and progression. In this study, we have generated RNASeq data from tumours arising in two established mouse models of prostate cancer, PB-Cre/PtenloxP/loxP and p53loxP/loxPRbloxP/loxP, and integrated this with published human prostate cancer expression data to pinpoint cancer-associated gene expression changes that are conserved between the two species. In order to identify potential therapeutic targets, we then filtered this information for genes that are either known or predicted to be druggable. Using this approach, we identified the serine/threonine kinase MELK as a potential therapeutic target in prostate cancer. MELK was overexpressed in both human and murine prostate cancers, and high expression of MELK was associated with biochemical recurrence in prostate cancer patients. Overall design: 92 Samples
Identification of potential therapeutic targets in prostate cancer through a cross-species approach.
Cell line, Subject
View SamplesImmunosenescence, the age-related decline in immune system function, is a general hallmark of aging. While much is known about the cellular and physiological changes that accompany immunosenescence, we know very little about the genetic influences on this phenomenon.
Age-specific variation in immune response in Drosophila melanogaster has a genetic basis.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Sexually dimorphic genome-wide binding of retinoid X receptor alpha (RXRα) determines male-female differences in the expression of hepatic lipid processing genes in mice.
Sex, Age, Specimen part
View SamplesAnalysis of gender differential gene expression levels in mouse liver.
Sexually dimorphic genome-wide binding of retinoid X receptor alpha (RXRα) determines male-female differences in the expression of hepatic lipid processing genes in mice.
Sex, Age, Specimen part
View SamplesVascular hypoperfusion is a pathological phenomenon in the glaucomatous optic nerve head. We report transcriptional responses in GFAP-negative LC cells exposed to in-vitro hypoxic stress (1%O2).
Hypoxia regulated gene transcription in human optic nerve lamina cribrosa cells in culture.
Specimen part
View SamplesTranscriptional changes upon elicitor treatment over time (0, 30, 60 min) have been analysed with the A.thaliana Landsberg (wt) and fls2-17 (flagellin receptor mutant).
Perception of the bacterial PAMP EF-Tu by the receptor EFR restricts Agrobacterium-mediated transformation.
Age, Compound, Time
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