Estrogen receptors (ERs), which mediate the proliferative action of estrogens in breast cancer cells, are ligand-dependent transcription factors that regulate expression of their primary target genes through several mechanisms. In addition to direct binding to cognate DNA sequences, ERs can be recruited to DNA through other transcription factors (tethering), or affect gene transcription through modulation of signaling cascades by non-genomic mechanisms of action. To better characterize the mechanisms of gene regulation by estrogens, we have identified more than 700 putative primary and more than 1500 putative secondary target genes of estradiol in MCF7 cells through microarray analysis performed in the presence or absence of the translation inhibitor cycloheximide.
Mechanisms of primary and secondary estrogen target gene regulation in breast cancer cells.
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View SamplesPhysical exercise training is a known protective factor against cardiovascular morbidity and mortality. Nevertheless, the underlying specific molecular mechanisms still remain uncompletely explored. To identify molecular mechanisms by which exercise training induces this favorable phenotype a genomic approach was used in an animal model of mild exercise previously demonstrated by our group to induce cardioprotection.
Gene expression profile of rat left ventricles reveals persisting changes following chronic mild exercise protocol: implications for cardioprotection.
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View SamplesMaintenance of vascular integrity in the adult animal is needed for survival and critically dependent on the endothelial lining, which controls barrier function, blood fluidity, and flow dynamics. However, nodal regulators that coordinate endothelial identity and function in the adult animal remain poorly characterized. Here we show that endothelial KLF2 and KLF4 control a large segment of the endothelial transcriptome thereby affecting virtually all key endothelial functions. Inducible endothelial-specific deletion of Klf2 and/or Klf4 reveals that a single allele of either gene is sufficient for survival, but absence of both (EC-DKO) results in acute death from myocardial infarction, heart failure, and stroke. EC-DKO animals exhibit profound compromise in vascular integrity and profound dysregulation of the coagulation system. Collectively, these studies establish an absolute requirement for KLF2/4 for maintenance of endothelial and vascular integrity in the adult animal. Overall design: Eight-to-ten-week old mice were intraperitoneally injected with tamoxifen to trigger endothelial-specific gene deletion of KLF2 and/or KLF4. At day 6 post-injection, endothelial cells were isolated from the heart and total RNA was purified.
KLF2 and KLF4 control endothelial identity and vascular integrity.
Specimen part, Subject
View SamplesSerotonin in the mammary gland is known to regulate processes such as calcium homeostasis, tight junction permeability, and milk protein gene expression. The objective of this study was to discover novel genes, pathways and functions which serotonin modulates during lactation. The rate-limiting enzyme in the synthesis of non-neuronal serotonin is tryptophan-hydroxylase (TPH1). Therefore, we used TPH1 knock-out mice dams (serotonin deficient) and compared them to wild-type dams and also Tph1 deficient dams injected daily with 5-HTP. Mammary gland tissues were collected on day 10 of lactation and then analyzed by RNA sequencing. Overall design: Genome-wide gene expression profiles of 12 mouse mammary gland samples were evaluated using RNA sequencing; these 12 samples belong to wild-type dams (WT; n = 4), Tryptophan hydroxylase (Tph1) knock-out dams (KO; Tph1 deficient; n = 4), and Tph1 deficient dams injected daily with 5-HTP (RC; n = 4). Mammary tissues were collected on day 10 of lactation and then underwent RNA extraction, library generation, and subsequent sequencing.
Transcriptomic Analysis of the Mouse Mammary Gland Reveals New Insights for the Role of Serotonin in Lactation.
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View SamplesPurpose: Here we describe the modulation of a gene expression program involved in cell fate. Methods: We depleted U2AF1 in human induced pluripotent stem cells (hiPSCs) to the level found in differentiated cells using an inducible shRNA system, followed by high-throughput RNAseq, revealing a gene expression program involved in cell fate determination. Results: Approximately 85% of the total raw reads were mapped to the human genome sequence (GRCh37), giving an average of 200 million human reads per sample for total RNA and 15 million human reads per sample for small RNA libraries. Conclusions: Our results show that transcriptional control of gene expression in hiPSCs can be set by the CSF U2AF1, establishing a direct link between transcription and AS during cell fate determination. Overall design: hiPSCs were differentiated into the three germ layers following the described protocol in the study (Gifford et al., 2013).
The core spliceosomal factor U2AF1 controls cell-fate determination via the modulation of transcriptional networks.
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View SamplesM cells are the main site of bacterial translocation in the intestine. We used the in vitro M cell model to study the effect of the commensal bacteria; Lactobacillus salivarius, Eschericha coli and Bacteroides fragilis, on M cell gene expression.
Differential intestinal M-cell gene expression response to gut commensals.
Specimen part, Treatment
View SamplesAllergic asthma is a complex trait. Several approaches have been used to identify biomarkers involved in this disease. This study aimed at demonstrating the relevance and validity of microarrays in the definition of allergic asthma expression pattern. The authors compared the transcript expressions of bronchial biopsy of 2 different microarray experiments done 2 years apart, both including nonallergic healthy and allergic asthmatic subjects (n = 4 in each experiment). U95Av2 and U133A GeneChips detected respectively 89 and 40 differentially expressed genes. Fifty-five percent of the U133A genes were previously identified with the U95Av2 arrays. The immune signaling molecules and the proteolytic enzymes were the most preserved categories between the 2 experiments, because 3/4 of the genes identified by the U133A were also significant in the U95Av2 study for both categories. These results demonstrate the relevance of microarray experiments using bronchial tissues in allergic asthma. The comparison of these GeneChip studies suggests that earlier microarray results are as relevant as actual ones to target new genes of interest, particularly in function categories linked to the studied disease. Moreover, it demonstrates that microarrays are a valuable technology to target novel allergic asthma pathways as well as biomarkers.
A comparison of two sets of microarray experiments to define allergic asthma expression pattern.
Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.
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View SamplesGene expression analyses were carried out to identify genes regulated by 17-beta estradiol (E2) and Hydroxytamoxifen (OHT) through GPR30 in SKBR3 cells, a breast cancer cell-line which expresses GPR30 but lacks Estrogen Receptor alpha or beta.
Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF.
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View SamplesAsthma pathogenesis and susceptibility involves a complex interplay between genetic and environmental factors.
Functional classes of bronchial mucosa genes that are differentially expressed in asthma.
Sex, Specimen part
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