Global analysis of p53-regulated transcription reveals its direct targets and unexpected regulatory mechanisms (microarray)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Mary Allen
PROVIDER: E-GEOD-53965 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-05-15 | E-GEOD-53966 | biostudies-arrayexpress
Project description:Diethlstilbestrol (DES) is a synthetic estrogen prescribed to several millions of pregnant women worldwide. The risk for breast cancer after age 40 in women prenatally exposed to DES has been reported, however, the precise mechanism of susceptibilities to breast cancer remains to be resolved. To understand the mechanism of effect of intrauterine exposure to DES on human mammary glands at peripubertal stage, we investigated the global gene expression profile of terminal end buds (TEBs), the target of carcinogen, in rat mammary glamds at postnatal days (PND) 35 and 49, equivalent to peripubertal stage in human, exposed to low or high dose of DES at neonatal period. In all group, the number of TEBs was gradually increased and peaked at PND35 and decreased at PND49. At PND 35 and 49, low dose of DES-treated group showed highest number of TEBs. At PND35, β- and γ-casein mRNA expression inreased 8.19-fold and 26.05-fold, respectively, and the most significant network revealed by IPA analyses showed relevance of NF-κB in low dose of DES-treated group. The present findings suggested that deregulation of mammary gland differentiation and development-related genes group may contribute to the increase of number of TEBs at critical period of carcinogen susceptibilities. Experiment: We used laser capture microdissection to specifically isolate the cells from terminal end buds (TEBs) in rat mammary gland at 35 and 49 days after birth. Inbred Sprague-Dawley female rats were subcutaneously given 0.05ml sesame oil (group I, control) and either 1 μg (group II) or 100 μg (group III) diethlstilbestrol (DES, Sigma Chemical Co., St. Louis, Mo. USA) dissolved in 0.05 ml sesame oil within 24 hr of birth. Animal were weaned at 21 days of birth and each group of rats was autopsied at 35 and 49 days of birth. From group I (35 days of birth: n=2, 49 days of birth: n=2), group II (35 days of birth: n=2, 49 days of birth: n=2), group III (35 days of birth: n=2, 49 days of birth: n=2), we performed a hybridization, respectively.
2010-11-06 | E-GEOD-25043 | biostudies-arrayexpress
Project description:This analysis utilised the \"Transformics Assay\" and evaluated the effect of cell exposure to 0.02 μg/ml of Benzo(a)pyrene, the lowest transforming concentration, using the BALB / c 3T3 A31-1-1 cell line. The Transformic assay is an integrated approach combining the Cell Transformation Assay (CTA), with the high throughput technology of transcriptomics. The CTA is a widely used in vitro assay that has been designed to evaluate the effects of chemicals on the growth of specific cell types and their potential progression through a transformation process from being normal cells to fully malignant cells. It has the potential to detect both genotoxic and some non-genotoxic carcinogens and shows a good correlation with rodent bioassay data. However lack of understanding of the mechanistic basis of the assays, and particularly of the mechanisms leading to cell malignancy, has limited its acceptance for regulatory purposes. The Transformics Assay introduces the RNA extraction and microarray experiment performed at specific time points along the process of in vitro transformation, helping to identify mechanisms of action leading to chemical-induced transformation. The experiment was conducted testing the carcinogen Benzo(a)pyrene (CAS No.50-32-8), which is a polycyclic aromatic hydrocarbon (PHA) and classified as carcinogenic to humans (Group 1) by IARC. Particularly Benzo(a)pyrene is a prototypical member of this class of chemicals and its toxic effects has been extensively studied, both in laboratory animals and human populations. Benzo(a)pyrene and others PAHs-induced carcinogenesis is a multi-step process, which since the last decade, was considered to be initiated and substantially sustained by the reaction and binding to DNA (oncogenic targets). Indeed, as other PHAs, Benzo(a)pyrene is metabolically activated to a series of reactive intermediates by CYP450 and related enzymes under control of the aryl-hydrocarbon receptor (AhR). These events support the genotoxic mode of carcinogenic action. Nevertheless it is now widely recognized that Benzo(a)pyrene can act via non-genotoxic modes of action too, including epigenetic mechanisms involving the AhR signaling pathway, oxidative stress, disruption of mitogenic and other cellular signaling. This study aimed to explore the molecular and cellular events necessary to sustain the transforming activity of Benzo(a)pyrene, at the lowest in vitro concentration capable of sustaining the process of oncotransformation. In order to find the lowest transforming concentration, a preliminary CTA has been conducted according to the EURL-ECVAM (EU Reference Laboratory European Centre for the Validation of Alternative Methods) validated protocol. The exposure time recommended by EURL-ECVAM, 72 hrs, represents both the exposure time of cells and the RNA extraction time point. According to previous studies 72 hrs exposure could be a critical timing to study the cell transformation process, during which differences in adverse and adaptive cell responses began to become visible at the transcriptional level.
2021-09-01 | E-MTAB-10405 | biostudies-arrayexpress
Project description:We used RNA-seq to determine the effects of AraC and arabinose on RNA levels genome-wide in S. enterica. Wild-type or delta araC mutant cells were grown in both the presence and absence of 0.2% L-arabinose. RNA-Seq libraries from two independent biological replicate samples were sequenced for (i) wild-type cells with no treatment, (ii) wild-type cells treated with arabinose, (iii) delta araC cells with no treatment, (iv) delta araC cells treated with arabinose. Comparisons were made between (i) and (ii) [analysis file name: Salmonella RNA-seq processed WT without arabinose vs WT with arabinose.xls], between (i) and (iii) [analysis file name: Salmonella RNA-Seq proessed no arabinose WT vs no arabinose delta araC.xls], and between (ii) and (iv) [analysis file name: Salmonella RNA-Seq processed arabinose WT vs arabinose delta araC.xls]. All analysis files are available from https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-1901/E-MTAB-1901.additional.1.zip
2013-10-04 | E-MTAB-1901 | biostudies-arrayexpress
Project description:We selected humann intervertebral disc samples to perform proteomics analysis. There were 1 case of grade I , 1 case of grade II, 3 cases of grade Ⅲ and 3 cases of grade Ⅳ according to Pfirrmann classfication. RNA seqencing analysis and single-cell RNA sequencing were integrated with proteomics data to identify the hub genes for intervertebral disc degeneration using bioinformatic method.
2023-05-10 | PXD040593 | Pride
Project description:Human pluripotent stem cells (hPSCs) such as embryonic stem cells and induced pluripotent stem cells are promising materials for cell-based regenerative therapies to heart diseases. However, until realization there are many hurdles such as high efficiency of cardiac differentiation of hPSCs and production of clinical-grade cardiac cells derived from hPSCs. Here, we show that a novel small molecule KY02111 robustly enhances differentiation to functional cardiomyocytes from hPSCs. To reveal how KY02111 function on promoting cardiac differentiation of hPSCs, we analyzed the gene expression profiles in KY02111-treated IMR90-1 hiPSCs using the microarray technique. At Day3 of cardiac differentiation from hiPSCs, KY02111 or DMSO was added in the culture and then the cell population was harvested after 12 or 24 hours for RNA extraction.
2012-10-30 | E-GEOD-33622 | biostudies-arrayexpress
Project description:Protein aggregation in the outermost layers of the cornea, leading to cloudy vision and in severe cases blindness, is linked to mutations in the extracellular matrix protein, transforming growth factor-β-induced protein (TGFBIp). Among the most frequent disease-causing mutations are R124H and R555W, both associated with granular corneal dystrophy (GCD) characterized by early-onset amorphous aggregation. The molecular mechanisms of protein aggregation in GCD are largely unknown. In this study, we determined the crystal structures of R124H and R555W. Whereas no structural changes of mutated monomeric TGFBIp can explain its aggregation propensity, the two mutations facilitate a new dimer interface in the crystal packing, not appearing in the wild-type structure. The interface in both R124H and R555W structures are centered on residue 124 in one TGFBIp molecule and 555 in a second TGFBIp molecule. This unique interface of R124H and R555W is not compatible with arginines at positions 124 and 555 as seen in wild-type TGFBIp. Hence, this intermolecular interaction may underlie the similar aggregation behavior exhibited by the two TGFBIp mutants in vivo. Using cross-linking mass spectrometry, we identified and characterized a dimer of TGFBIp wild-type and mutants in solution. The soluble dimers also involve interactions between the N- and C-terminal domains of two TGFBIp molecules but is not identical to the crystal packing dimer interface involving R124H and R555W. Targeting of the crystal packing dimer interface might offer new opportunities for therapeutic intervention to treat patients with GCD.
2021-09-08 | PXD022976 | Pride
Project description:Affymetrix 500K array was used to determine gross genomic aberrations in a panel of Primary Effusion Lymphoma (PEL) cell lines, specifically focusing on chromosome 10, which includes the Phosphatase and Tensin Homolog (PTEN) locus. 10 PEL cell lines were hybridized to the Affymetrix 500K array where non-PEL B-cell lymphoma cell lines BJAB and DG75 were used as controls. The data was analyzed using Partek Genomic Suite software and compared to normal tonsil controls.
2011-06-23 | E-GEOD-28684 | biostudies-arrayexpress
Project description:To determine genes in FL HSCs that are sensitive to Notch signagling, E14.5 FL cells were cultured on DL1( to stimulate Notch signaling). Cells were cultured in the presence of DMSO (vehicle control) or gamma secretase inhibitor (1uM) for 4 hrs or 10hrs. Gamma secretase inhibitor was used to inhibit Notch signaling. SLAM-LSKs were sorted and used for RNA preparation. 7 biological replicates (14 totalt samples) were collected for cells cultured for 4hrs. 4 biological replicates (8 total samples) were collected from cells cultured for 10hrs. Each replicate consisted of a DMSO and GSI treated sample
2014-01-28 | E-GEOD-53713 | biostudies-arrayexpress
Project description:The Nodal/Activin morphogens are secreted signaling molecules that form concentration gradients during early embryogenesis providing stem cells with positional information and differentiation instructions important for embryonic patterning. The molecular basis driving stem cell interpretation of signaling gradients and the undertaking of distinct cell fate decisions remains poorly understood. We show that perturbation of endogenous Nodal/Activin signaling in ES cells leads to exit from self renewal towards mesendodermal differentiation at high signaling and trophectoderm induction during low signaling. ChIP-seq of Phospho-Smad2, the downstream transcription factor of the Nodal/Activin pathway reveals binding to distinct subsets of target genes in a dose dependent manner including the promoter region of the Oct4 master regulator of stemness. Consequently, both Oct4 mRNA and protein levels are directly driven by graded Nodal/Activin signaling. Hence stem cells interpret and carry out differential Nodal/Activin signaling instructions via a corresponding gradient of Smad2 phosphorylation that selectively titers self renewal against alternative differentiation programs. 3 pSmad2 ChIP samples corresponding to ES cells pretreated for 6 hours in 10uM SB followed by 18 hours in 25ng/ml Activin, 1/5000 DMSO and 10uM SB in 20% KSR media. Controls include the corresponding input DNA for each treatment.
2011-01-31 | E-GEOD-23581 | biostudies-arrayexpress