To investigate the molecular mechanisms associated with initial dose-related events that are linked to the development of liver tumours: liver growth; cell proliferation; changes in histopathology such as hypertrophy
An integrated functional genomic study of acute phenobarbital exposure in the rat.
Specimen part, Time
View SamplesThe LEF/TCF family of transcription factors are downstream effectors of the WNT signaling pathway, which drives colon tumorigenesis. LEF/TCFs have a DNA sequence-specific HMG box that binds Wnt Response Elements (WREs). The E tail isoforms of TCFs are alternatively spliced to include a second DNA binding domain called the C-clamp. We show that induction of a dominant negative C-clamp version of TCF1 (dnTCF1E) induces a p21-dependent stall in the growth of DLD1 colon cancer cells. Induction of a C-clamp mutant did not induce p21 or stall cell growth. Microarray analysis revealed that induction of p21 by dnTCF1EWT correlated with a decrease in expression of p21 suppressors that act at multiple levels from transcription (SP5, YAP1, RUNX1), to RNA stability (MSI2), and protein stability (CUL4A). We show that the C-clamp is a sequence specific DNA binding domain that can make contacts with 5-RCCG-3 elements upstream or downstream of WREs. The C-clamp-RCCG interaction was critical for TCF1E mediated transcriptional control of p21-connected target gene promoters. Our results indicate that a WNT/p21 circuit is driven by C-clamp target gene selection.
A WNT/p21 circuit directed by the C-clamp, a sequence-specific DNA binding domain in TCFs.
Specimen part
View SamplesWe used microarray analysis to profile the function of TCF7L1 in human embryonic stem cells.
TCF7L1 suppresses primitive streak gene expression to support human embryonic stem cell pluripotency.
Cell line
View SamplesWe used microarray analysis to profile the function of TCF7L1 in human embryonic stem cells.
TCF7L1 suppresses primitive streak gene expression to support human embryonic stem cell pluripotency.
Specimen part, Cell line
View SamplesFe deficiency stimulates a coordinated response involving reduction, transport and redistribution of Fe in the roots. The expression of genes regulated by Fe deficiency in the two contrasting Arabidopsis thaliana ecotypes, Tsu-1 and Kas-1, shows that different ecotypes can respond in diverse ways, with different Fe regulated overrepresented categories.
Use of natural variation reveals core genes in the transcriptome of iron-deficient Arabidopsis thaliana roots.
Age, Specimen part, Time
View SamplesPurpose: Aim of the study is to identify functional differences between the P1 and P2-HNF4a isoforms. To do this, we generated Tet-On inducible lines that express either the human (P1) HNF4a2 or (P2) HNF4a8 under control of DOX in the HCT116 human colon cancer cells. Methods: HNF4a2 and Parental lines were induced with 0.3 µg/mL DOX, while HNF4a8 line was induced with either 0.1 or 0.3 µg/mL DOX for 24 hours. Samples were generated by deep sequencing, using the Illumina TruSeq RNA. Result: There were common and unique dysregulated genes identified in the HNF4a2 and HNF4a8 lines (+DOX); more upregulated genes than downregulated genes in both the lines. Conclusion: The functional difference between HNF4a2 and HNF4a8 is that the latter tends to upregulate genes involved in proliferation and anti-apoptosis while HNF4a2 upregulates genes involved in growth suppression and cell death. Overall design: Tet-On inducible HCT116 cell (Parental, HNF4a2, and HNF4a8) lines, treated with (0.0, 0.1, or 0.3 µg/mL) DOX for 24 hours, were 50bp pair-ended sequenced in triplicate using Illumina TruSeq RNA Sample Prep v2 Kit.
Differential Effects of Hepatocyte Nuclear Factor 4α Isoforms on Tumor Growth and T-Cell Factor 4/AP-1 Interactions in Human Colorectal Cancer Cells.
No sample metadata fields
View SamplesThe objective of this study was to examine the effect of dietary restriction and subsequent re-alimentation induced compensatory growth on the global gene expression profile of jejunum epithelial Holstein Friesian bulls (n=40) were assigned to one of two groups: restricted feed allowance (RES; n=20) for 125 days (Period 1) followed by ad libitum access to feed for 55 days (Period 2) or (ii) ad libitum access to feed throughout (ADLIB; n=20). All bulls received the same diet of 70% concentrate 30% grass silage through out the experimental trial,with the amount of feed provided different dependent on each treatment group. At the end ofeach period, 10 animals from each treatment group (RES, ADLIB) were slaughtered, and jejunum epithelial collected from all animals. RNA was extracted and jejununal epithelium gene expression was examined using RNAseq technology on all samles collected (end of Period 1: 10 samples each from ADLIB and RES groups; end of Period 2: 10 samples each from ADLIB and RES groups). Dietary restriction and subsequent re-alimentation were associated with altered expression of genes involved in digestion and metabolism, aswell as cellular protection and detoxification in jejunal epithelia. This information may be exploited in genomic breeding programmes to assist selection of cattle with a greater ability to compensate following a period dietary restriction. Overall design: 40 jejunumal epithelium RNA samples were analysed in total. 10 samples were from jejunum epithelium collected at the end of a period of dietary restriction (d 125; Period 1) and 10 samples were from jejunum epithelium collected after 55 days of compensatory growth (d 55 of re-alimentation, Period 2). In addition, RNA was also anlaysed from 10 samples collected from animals fed ad libitum at the end of both Period 1 and Period 2.
Gene co-expression networks contributing to the expression of compensatory growth in metabolically active tissues in cattle.
Specimen part, Subject
View SamplesThe objective of this study was to examine the effect of dietary restriction and subsequent re-alimentation induced compensatory growth on the global gene expression profile of ruminal epithelial papillae. Holstein Friesian bulls (n=38) were assigned to one of two groups: restricted feed allowance (RES; n=19) for 125 days (Period 1) followed by ad libitum access to feed for 55 days (Period 2) or (ii) ad libitum access to feed throughout (ADLIB; n=19). All bulls received the same diet of 70% concentrate 30% grass silage through out the experimental trial,with the amount of feed provided different dependent on each treatment group. At the end of Period 1, 9 animals from each treatment group were slaughtered, with 10 animals from each treatment slaughtered at the end of Period 2. Rumen epithelium was collected from all animals within thirty minutes of slaughter. RNA was extracted and rumen epithelium gene expression was examined using RNAseq technology on all samles collected (end of Period 1: 9 samples each from ADLIB and RES groups; end of Period 2: 10 samples each from ADLIB and RES groups). Genes identified as differentially expressed in response to both dietary restriction and subsequent compensatory growth included those involved in processes such as cellular interactions and transport, protein folding and gene expression, as well as immune response. This information can be exploited in genomic breeding programmes to assist selection of cattle with a greater ability to compensate following a period dietary restriction. Overall design: 38 rumen epithelium RNA samples were analyzed in total. Purebred Holstein Friesian bulls were assigned to one of two feeding treatments (i) restricted feed allowance for 125 days (n=9) followed by ad libitum access to feed for a further 55 days (n=10) or (ii) a control group with ad libitum access to feed through out the 180 days trial (n=19). The first 125 days of the trial were denoted as Period 1, during which treatment groups were fed differentially. The subsequent 55 days, denoted as Period 2 during which all bulls were fed ad libitum. All bulls received the same diet of 70% concentrate 30% grass silage through out the experimental trial, with the amount of feed provided different dependent on each treatment group. Restricted fed animals were fed to grow at 0.6 kg /day during Period 1, with ad libitum animals expected to gain in excess of 1.5 to 2 kg/day.
Gene co-expression networks contributing to the expression of compensatory growth in metabolically active tissues in cattle.
Sex, Specimen part, Subject
View SamplesIron (Fe) is an essential plant micronutrient, and its deficiency limits plant growth and development on alkaline soils. Under Fe deficiency, plant responses include upregulation of genes involved in Fe uptake from the soil. However, little is known about shoot responses to Fe deficiency. Using microarrays to probe gene expression in Kas-1 and Tsu-1 ecotypes of Arabidopsis thaliana revealed conserved rosette gene expression responses to Fe deficiency. Fe regulated genes included known metal homeostasis-related genes, and a number of genes of unknown function.
Rosette iron deficiency transcript and microRNA profiling reveals links between copper and iron homeostasis in Arabidopsis thaliana.
Time
View SamplesHere we examine the regulation of cell death by hepatic leukemia factor (HLF), which is an output regulator of circadian rhythms and is aberrantly expressed in human cancers, using an ectopic expression strategy in JB6 mouse epidermal cells and human keratinocytes. Ectopic HLF expression inhibited cell death in both JB6 cells and human keratinocytes, as induced by serum-starvation, tumor necrosis factor alpha and ionizing radiation.
Hepatic leukemia factor promotes resistance to cell death: implications for therapeutics and chronotherapy.
Cell line
View Samples