This SuperSeries is composed of the SubSeries listed below.
Genome-wide targeting of the epigenetic regulatory protein CTCF to gene promoters by the transcription factor TFII-I.
Specimen part, Cell line
View SamplesAnalysis of the effect of TFII-I depletion on gene expression Wehi-231 cell lines.
Genome-wide targeting of the epigenetic regulatory protein CTCF to gene promoters by the transcription factor TFII-I.
Specimen part, Cell line
View SamplesSnail1 transcriptional factor is essential for triggering epithelial-to-mesenchymal transition (EMT) and inducing tumor cell invasion. We report here that Snail1 plays also a key role in tumor associated fibroblasts since is necessary for enhancement by these cells on epithelial cells tumor invasion. Snail1 expression in fibroblast requires signals derived from tumor cells such as TGF-b; reciprocally, in fibroblasts Snail1 organizes a complex program that favors collective invasion of epithelial cells at least in part by the secretion of diffusible signaling molecules, such as prostaglandin E2. The capability of human or murine tumor-derived cancer associated fibroblasts to promote tumor invasion is associated to Snail1 expression and obliterated by Snail1 depletion. In vivo experiments show that tumor cells co-transplanted with Snail1 depleted fibroblasts show lower invasion than those xenografted with control fibroblasts. Finally Snail1 depletion in mice prevents the formation of breast tumors and decreased their invasion. Therefore, these results demonstrate that the role of Snail1 in tumor invasion is not limited to its effect in EMT but dependent on its expression in stromal fibroblasts where it orchestrates its activation and the crosstalk with epithelial cells.
Snail1-Dependent Activation of Cancer-Associated Fibroblast Controls Epithelial Tumor Cell Invasion and Metastasis.
Specimen part
View SamplesTo understand the fruit changes and mechanisms involved in the compatible grapevine-virus interaction, we analyzed the berry transcriptome in two stages of development (veraison and ripening) in the red wine cultivar Cabernet Sauvignon infected with Grapevine leaf-roll-associated virus-3 (GLRaV-3). Analysis of global gene expression patterns indicate incomplete berry maturation in infected berries as compared to uninfected fruit suggesting viral infection interrupts the normal berry maturation process.
Compatible GLRaV-3 viral infections affect berry ripening decreasing sugar accumulation and anthocyanin biosynthesis in Vitis vinifera.
Age, Specimen part
View SamplesSilicosis, a fibrotic granulomatous lung disease, may occur through accidental high-dose or occupational inhalation of silica, leading to acute/accelerated and chronic silicosis, respectively. While chronic silicosis has a long asymptomatic latency, lung inflammation and apoptosis are hallmarks of acute silicosis. In animal models, histiocytic granulomas develop within days after high-dose intratracheal silica instillation. However, following chronic inhalation of occupationally relevant doses of silica, discrete granulomas resembling human silicosis arise months after the final exposure without significant lung inflammation/apoptosis. To identify molecular events associated with chronic silicosis, lung RNAs from controls or chronically silica-exposed rats were analyzed by Affymetrix at 28 wk after silica exposures. Results suggested a significant upregulation of 144 genes and downregulation of seven genes. The upregulated genes included complement cascade, chemokines/chemokine receptors, G-protein signaling components, metalloproteases, and genes associated with oxidative stress. To examine the kinetics of gene expression relevant to silicosis, qPCR, ELISA, Luminex-bead assays, Western blotting, and/or zymography were performed on lung tissues from 4 d, 28 wk, and intermediate times after chronic silica exposure and compared with 14 d acute silicosis samples. Results indicated that genes regulating fibrosis (secreted phosphoprotein-1, CCL2, and CCL7), redox enzymes (superoxide dismutase-2 and arginase-1), and the enzymatic activities of matrix metalloproteinases 2 and 9 were upregulated in acute and chronic silicosis; however, proinflammatory cytokines were strongly upregulated only in acute silicosis. Thus, inflammatory cytokines are associated with acute but not chronic silicosis; however, genes regulating fibrosis, oxidative stress, and metalloproteases may contribute to both acute and chronic silicosis.
Fibrogenic and redox-related but not proinflammatory genes are upregulated in Lewis rat model of chronic silicosis.
Specimen part, Treatment
View SamplesIn rice (Oryza sativa L.), the haplotype at the multigenic SUBMERGENCE 1 (SUB1) locus determines survival of prolonged submergence. SUB1 encodes two or three group VII Ethylene Response Factor (ERF) family transcription factors, SUB1A, SUB1B and SUB1C. A highly submergence-inducible SUB1A allele is present in lines that are submergence tolerant. This gene is the determinant of submergence tolerance. Here, the heterologous ectopic expression of rice SUB1A and SUB1C in Arabidopsis thaliana was employed to assess the transcriptional network mobilized by ectopic expression of SUB1A and SUB1C.
Expression of rice SUB1A and SUB1C transcription factors in Arabidopsis uncovers flowering inhibition as a submergence tolerance mechanism.
Specimen part
View SamplesKlotho is critical for the survival of triple negative breast cancer (TNBC) cells HCC1395, since its depletion leads to decreased cell viability, cell cycle arrest and apoptosis.
γKlotho is a novel marker and cell survival factor in a subset of triple negative breast cancers.
Specimen part, Cell line
View SamplesDermal lymphatics form a network that connects all the hair follicles in skin and localize in proximity to the Hair Follicle Stem Cell. RNA sequencing analyses of isolated dermal lymphatics at two different time points of the hair follicle cycle (P55 and P70) indicate the existence of dynamic signaling networks associated with lymphatic remodeling, immune trafficking, and HF signaling. Overall design: Prox1CreERT2; ROSA26-LSL-eYFP mice of P55 (Mid Telogen) and P70 (Late telogen) were sacrificed and eYFP positive cells were isolated from the backskin.
Lymphatic vessels interact dynamically with the hair follicle stem cell niche during skin regeneration in vivo.
Treatment, Subject
View SamplesMammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a critical regulator of cell growth by integrating multiple signals (nutrients, growth factors, energy and stress) and is frequently deregulated in many types of cancer. We used a robust experimental paradigm involving the combination of two interventions, one genetic and one pharmacologic to identify genes regulated transcriptionally by mTORC1. In Tsc2+/+, but not Tsc2-/- immortalized mouse embryo fibroblasts (MEFs), serum deprivation downregulates mTORC1 activity. In Tsc2-/- cells, abnormal mTORC1 activity can be downregulated by treatment with rapamycin (sirolimus). By contrast, rapamycin has little effect on mTORC1 in Tsc2+/+ cells in which mTORC1 is already inhibited by low serum. Thus, under serum deprived conditions, mTORC1 activity is low in Tsc2+/+ cells (untreated or rapamycin treated), high in Tsc2-/- cells, but lowered by rapamycin; a pattern referred to as a low/low/high/low or LLHL, which allowed the identification of genes regulated by mTORC1 by performing the appropriate comparisons
Regulation of TFEB and V-ATPases by mTORC1.
Specimen part, Treatment
View SamplesHaCat cell cycle experiment: During the somatic cell cycle, DNA and epigenetic modifications in DNA and histones are copied to daughter cells. DNA replication timing is tightly regulated and linked to GC content, chromatin structure, andgene transcription, but how maintenance of histone modifications relates to replication timing and transcription is less understood.The gene expression patters on HaCaT keratinocytes during the cell cycle is studied by a time series analysis of synchroniced cells sampled at 3 hour intervals. We show that genes enriched with the repressive chromatin mark histone H3 lysine 27 tri-methylation are transcribed during DNA replication . The gene expression is related to replication timing, as genes expressed during G1/S transition andearly S phase generally have higher GC content and are replicated earlier than genes expressed during late S phase. These results indicate widespread replication-dependent expression in mammals and support a role for replication in transiently activating transcription of epigenetically silenced genes.
Transcription profiling during the cell cycle shows that a subset of Polycomb-targeted genes is upregulated during DNA replication.
Specimen part, Cell line, Time
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