The LIM-only protein FHL2 acts as a transcriptional modulator that positively or negatively regulates multiple signaling pathways. We recently reported that FHL2 cooperates with CBP/p300 in the activation of -catenin/TCF target gene cyclin D1. In this paper, we demonstrate that FHL2 is associated with the cyclin D1 promoter at the TCF/CRE site, providing evidence that cyclin D1 is a direct target of FHL2. We show that deficiency of FHL2 greatly reduces the proliferative capacity of spontaneously immortalized mouse fibroblasts which is associated with decreased expression of cyclin D1 and p16INK4a, and hypophosphorylation of Rb. Reexpression of FHL2 in FHL2-null fibroblasts efficiently restores cyclin D1 levels and cell proliferative capacity, indicating that FHL2 is critical for cyclin D1 activation and cell growth. Moreover, ectopic cyclin D1 expression is sufficient to override growth inhibition of immortalized FHL2-null fibroblasts. Gene expression profiling revealed that FHL2 deficiency triggers a broad change of the cell cycle program that is associated with downregulation of several G1/S and G2/M cyclins, E2F transcription factors and DNA replication machinery, thus correlating with reduced cell proliferation. This change also involves downregulation of the negative cell cycle regulators, particularly INK4 inhibitors, which could counteract the decreased expression of cyclins, allowing cells to grow. Our study illustrates that FHL2 can act on different aspects of the cell cycle program to finely regulate cell proliferation.
The LIM-only protein FHL2 regulates cyclin D1 expression and cell proliferation.
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The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory.
Specimen part, Treatment
View SamplesImmunological memory is generally thought to be mediated exclusively by lymphocytes such as memory T and B cells. However, enhanced innate immune responses caused by a previous infection increase protection against reinfection suggesting the presence of innate immunological memory. Here, we describe expression profile of peritoneal macrophages from wild-type mice pre-administrated with TLR ligands or from ATF7 knockout mice. ATF7 suppresses a group of innate-immunity genes in macrophage by recruiting H3K9 dimethyltransferase G9a. TLR ligands induce ATF7 phosphorylation, leading to release of ATF7 from chromatin and reduction in H3K9me2 level. Partially disrupted chromatin structure and increased basal expression on target genes are maintained for a long period, increasing resistance pathogens. Therefore we speculate ATF7 is important factor in controlling innate immunological memory.
The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory.
Specimen part
View SamplesMitochondrial biogenesis and metabolism recently emerged as critical modulators of stemness properties and differentiation programmes. The increase in mitochondrial biogenesis and metabolic shift toward increased oxidative phosphorylations (OXPHOS) appear as hallmarks of stem cell differentiation processes. While several mechanisms support the involvement of mitochondrial biogenesis and function in the regulation of stem cell differentiation, the mechanisms triggering mitochondrial biogenesis in the context of cell differentiation remain elusive. In this study, we performed transcriptomic and bioinformatic analyses in order to get deeper insights into the cross-regulation of mitochondrial biogenesis and hepatogenic differentiation of human bone marrow mesenchymal stem cells (BM-MSCs). We identified a transcriptional regulatory network involved in the co-regulation of stem cell differentiation and mitochondrial biogenesis. Overall design: Transcriptomics analyses performed at early time points of the hepatogenic differentiation of BM-MSC
MPV17 does not control cancer cell proliferation.
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View SamplesComparison of normal neuroblasts with malignant neuroblastomas (low- and high-stage)
Human fetal neuroblast and neuroblastoma transcriptome analysis confirms neuroblast origin and highlights neuroblastoma candidate genes.
Sex, Specimen part, Disease, Disease stage, Subject
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Genomic and transcriptomic comparison of post-radiation versus sporadic sarcomas.
No sample metadata fields
View SamplesNo description.
Genomic and transcriptomic comparison of post-radiation versus sporadic sarcomas.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesThe goal of this study was to investigate the effects of vairous diets on the expression of genes involved in intermediary metabolism in liver. Adult wild type male mice (3 for each group) were fed with the corresponding diet for two weeks, and then liver samples were collected. Total RNA was isolated by the RNAzol B reagent, and pellet was disolved in DEPC-treated water. Total RNA was isolated using RNA Bee reagent (Tel-Test Inc., Friendswood, TX) per the manufacturers protocol. RNA concentrations were quantified using a NanoDrop Spectrophotometer (NanoDrop Technologies, Wilmington, DE) at a wavelength of 260 nm. The integrity of the total RNA samples was evaluated by formaldehyde-agarose gel electrophoresis, and confirmed by visualization of 18S and 28S rRNA bands. The gene expression was determined by Affymetrix Mouse 430 2.0 Gene Expression Microarray. Nine different diets were used: Diet 1. TD.84224. EFA Deficient diet; Diet 2. TD 97070. High fat diet: Diet 3. TD.88137. Adjusted Calories Diet (42% from fat) (Western Diet); Diet 4. TD.02028. Atherogenic Rodent Diet; Diet 5. TD.89247. 60% Fructose Diet; Diet 6. TD.94048. AIN-93M Purified Diet, Diet 7. Current rodent diet used in LAR; Diet 8. DHA-supplemented diet; Diet 9. Diet-restriction: 75% of the diet consumed by ad lib feeding. Mice (n=3/diet) were fed one of these diets (Harlan Laboratories) for 3 weeks. All mice were euthanized in the morning (8:0010:00 A.M.) and blood and tissue samples were collected. All procedures were approved in accordance with Institutional Animal Care and Use Committee guidelines.
Effect of diet on expression of genes involved in lipid metabolism, oxidative stress, and inflammation in mouse liver-insights into mechanisms of hepatic steatosis.
Sex, Age, Specimen part
View SamplesWe report the effects of exposure to the endocrine disurptor (2-ethylhexyl) phthalate (DEHP) on transcriptome modification in the livers of in vivo Zebrafish. Our data indicate changes in fatty acid metabolism and insulin resistance, pathways associated with the development of Non-Alcoholic Fatty Liver Disease (NAFLD). Overall design: Examination of transcriptome changes in an in vivo model organism exposed to a common, environmental compound.
Systems Analysis of the Liver Transcriptome in Adult Male Zebrafish Exposed to the Plasticizer (2-Ethylhexyl) Phthalate (DEHP).
No sample metadata fields
View SamplesThe approval of genetically modified (GM) crops is preceded by years of intensive research to demonstrate safety to humans and environment. We recently showed that in vitro culture stress is the major factor influencing proteomic differences of GM vs. non-GM plants. This made us question the number of generations needed to erase such memory. We also wondered about the relevance of alterations promoted by transgenesis as compared to environment-induced ones.
Environmental stress is the major cause of transcriptomic and proteomic changes in GM and non-GM plants.
Specimen part
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