Estrogen-Related Receptor alpha (ERR) is a nuclear receptor that acts principally as a regulator of metabolism processes particularly in tissues subjected to high-energy demand. Besides its implication in energy metabolism and mitochondrial biogenesis, ERR was recently associated with tumorigenesis. Notably, increased expression of ERR was noted in different cancerous tissues as breast, ovary and colon. However, supplemental studies are required to better understand the role of ERR in colon carcinoma.
ERRα metabolic nuclear receptor controls growth of colon cancer cells.
Cell line, Treatment
View SamplesRetinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Several breast cancer cells respond to the antiproliferative effects of RA, but others are RA-resistant. In several cases resistance has been correlated to the amplification of the erb-b2 receptor tyrosine kinase 2 (ERBB2) gene, but the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here we compared two human breast cancer cell lines, the MCF7 cell line, which responds to the antiproliferative action of RA and the BT474 cell line, which is RA-resistant subsequent to ERBB2 amplification in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes. Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated after RA addition. The paradigm of these proteins is the RA receptor a (RARa), which was phosphorylated in MCF7 cells but not in BT474 cells. The panel of the RA-regulated genes was also different. Overall our results indicate that ERBB2 amplification interferes with the ability of RA to activate kinases with consequences on the phosphorylation of several proteins involved in transcription and thus on gene expression. Overall design: Two human breast cancer cell lines were compared for their repertoire of genes regulated by retinoic acid (RA): the RA sensitive MCF7 cell line and the RA resistant B7474 cell line
Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines.
Specimen part, Cell line, Treatment, Subject
View SamplesWe sequenced mRNA from 3 neutrophil cells taken from 3 male adult to generate the gene expression profile of human neutrophil cells Overall design: Examination of mRNA levels in human neutrophils.
Disease-Associated Single-Nucleotide Polymorphisms From Noncoding Regions in Juvenile Idiopathic Arthritis Are Located Within or Adjacent to Functional Genomic Elements of Human Neutrophils and CD4+ T Cells.
No sample metadata fields
View SamplesIn depth temporal profiling of transcript changes at 10 time points during germination in Arabidopsis seed was carried out. The time course utilised, encompassed seed maturation, stratification, germination and post-germination and provided a global investigation into the tightly regulated, phasic changes that define seed germination.
In-depth temporal transcriptome profiling reveals a crucial developmental switch with roles for RNA processing and organelle metabolism that are essential for germination in Arabidopsis.
Specimen part, Disease, Time
View SamplesHepatocyte-nuclear-factor-4 (Hnf4) is a transcription factor that controls epithelial cell polarity and maturation during embryogenesis. Hnf4 conditional deletion during post-natal development results in minor consequences on intestinal epithelium integrity but promotes activation of the Wnt/-catenin pathway. Here we show that Hnf4 does not act as a tumor suppressor gene but is crucial to promote gut tumorigenesis in mice. Polyp multiplicity in ApcMin mice that lacks Hnf4 is suppressed in comparison to littermate ApcMin controls. Analysis of microarray gene expression profiles from mice lacking Hnf4 in the intestinal epithelium identifies its novel function in regulating the expression of reactive oxygen species (ROS) detoxifying genes. This role is supported with the demonstration that HNF4 is functionally involved in the protection against spontaneous and 5-fluorouracil chemotherapy-induced production of intracellular ROS in colorectal cancer cell lines. The analysis of a colorectal cancer patient cohort establishes that HNF4 is significantly up-regulated at both gene transcript and protein levels in tumors relative to adjacent benign epithelial resections. Several genes involved in ROS neutralization are also up-regulated in correlation with HNF4 expression. All together, the findings point to the nuclear receptor HNF4 as a potential therapeutic target to eradicate aberrant epithelial cell resistance to ROS production during intestinal tumorigenesis.
Hepatocyte nuclear factor-4alpha promotes gut neoplasia in mice and protects against the production of reactive oxygen species.
Specimen part
View SamplesAs macrophages are the primary site of Mtb infection and are sites of vitamin D signaling, we have used these cells to understand the molecular mechanisms underlying modulation of the immune response by the hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25D).
Vitamin D induces interleukin-1β expression: paracrine macrophage epithelial signaling controls M. tuberculosis infection.
Cell line
View SamplesInflorescence stages 1 to 12 from mutants involved in Arabidopsis small RNA metabolism. Three biological replicates of each mutant comprising at least 9 independent plants were harvested, and the expression profiles were determined using Affymetrix ATH1 arrays. Comparisons among the sample groups allow the identification of genes regulated by small RNAs (microRNAs and siRNAs).
microRNA-directed phasing during trans-acting siRNA biogenesis in plants.
No sample metadata fields
View SamplesAnalysis of changes in global transcript abundance profiles of 2 week old tim23 OE (overexpressor) and tim23 KO (knock-out) mutant Arabidopsis plants complared to wild-type (Col-0) using Affymetrix GeneChipル Arabidopsis ATH1 Genome Arrays.
Dual location of the mitochondrial preprotein transporters B14.7 and Tim23-2 in complex I and the TIM17:23 complex in Arabidopsis links mitochondrial activity and biogenesis.
Age, Specimen part
View SamplesTranscriptional regulatory networks (TRNs) provide insight into cellular behavior by describing interactions between transcription factors (TFs) and their gene targets. The Assay for Transposase Accessible Chromatin (ATAC)-seq, coupled with transcription-factor motif analysis, provides indirect evidence of chromatin binding for hundreds of TFs genome-wide. Here, we propose methods for TRN inference in a mammalian setting, using ATAC-seq data to influence gene expression modeling. We rigorously test our methods in the context of T Helper Cell Type 17 (Th17) differentiation, generating new ATAC-seq data to complement existing Th17 genomic resources (plentiful gene expression data, TF knock-outs and ChIP-seq experiments). In this resource-rich mammalian setting our extensive benchmarking provides quantitative, genome-scale evaluation of TRN inference combining ATAC-seq and RNA-seq data. We refine and extend our previous Th17 TRN, using our new TRN inference methods to integrate all Th17 data (gene expression, ATAC-seq, TF KO, ChIP-seq). We highlight new roles for individual TFs and groups of TFs (“TF-TF modules”) in Th17 gene regulation. Given the popularity of ATAC-seq (a widely adapted protocol with high resolution and low sample input requirements), we anticipate that application of our methods will improve TRN inference in new mammalian systems and be of particular use for rare, uncharacterized cell types. Overall design: Gene expression (RNA-seq) of naive and Th17- and Th0-polarized CD4 T Cells
Leveraging chromatin accessibility for transcriptional regulatory network inference in T Helper 17 Cells.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation.
Specimen part, Treatment, Time
View Samples