SREBP1c and mock virus expression profiles in AG01518 human fibroblasts
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE6877 | GEO | 2007/04/26
SECONDARY ACCESSION(S): PRJNA99079
REPOSITORIES: GEO
Similar Datasets
Project description:Oncogenic transformation alters the metabolism of cellular lipids to sustain tumor growth. We define a reciprocal mechanism by which cholesterol metabolism controls the formation and differentiation of pancreatic ductal adenocarcinoma (PDAC). Disruption of distal cholesterol biosynthesis by conditional inactivation of Nsdhl, or treatment with cholesterol-lowering statins caused murine pancreatic carcinomas induced by KrasG12D expression and homozygous Trp53 loss to undergo a differentiation switch from a glandular to basal (mesenchymal) phenotype. In parallel, PDACs from patients receiving statins had enhanced mesenchymal features. Mechanistically, statins and NSDHL loss induced sterol response element binding protein 1 (SREBP1), promoting autocrine transforming growth factor beta (TGF) signaling, inducing epithelial-mesenchymal transition. Activation of promesenchymal TGFβ effectors by cholesterol-lowering statins may select for poorly differentiated carcinomas.
2020-08-14 | GSE156210 | GEO
Project description:Linear tetrapyrrole (bilin)-based phytochrome sensors optimize photosynthetic light capture by mediating massive gene reprogramming in land plants, yet surprisingly, many sequenced chlorophyte (green) algae lack phytochrome genes. Previous studies on the heme oxygenase (hmox1) mutant of Chlamydomonas reinhardtii suggest that bilin biosynthesis in plastids is needed for regulation of a limited nuclear gene network implicated in oxygen detoxification during dark to light transitions. The hmox1 mutant is unable to grow photoautotrophically and poorly acclimates to increased illumination even in the presence of acetate. Here we show that these phenotypes reflect the reduced accumulation of PSI reaction centers as well as a loss of PSI and PSII antennae complexes during photoacclimation. Phenotypically, the hmox1 mutant is similar to the chlorophyll biosynthesis mutants, gun4, crd1 and cth1. However, many of the hmox1 phenotypes can be rescued by the application of exogenous biliverdin IXα, the bilin product of HMOX1; this rescue is independent of photosynthesis but strongly dependent upon blue light. RNA-Seq comparisons of hmox1, 4A+ wild type and two genetically complemented lines also reveal that bilins restore regulation of a small network of photosynthesis-associated nuclear genes. These include genes responsible for chlorophyll biosynthesis (CHLI1/2), PSI light-harvesting (LHCA4) and naphthoquinone metabolism (MEN2), all of which show reduced photoinduction in the hmox1 mutant. We propose that a bilin-based, blue light sensory system is responsible for the maintenance of a functional photosynthetic apparatus in light-grown C. reinhardtii. This critical and possibly ancestral role for bilins may be responsible for retention of bilin biosynthesis in all eukaryotic photosynthetic species.
2019-01-24 | GSE77388 | GEO
Project description:Neonatal rat ventricular cardiomyocytes (NRVCMs) were stretched biaxially (112%/24h) or stimulated with phenylephrine (PE, 50 uM), both resulting in a similar degree of hypertrophy. Unstretched NRVCMs served as negative control. Affymetrix microarray analysis revealed 164 genes more than 2.0-fold up- and 21 genes less than 0.5-fold downregulated (p<0.01). Differential expression was confirmed by real-time PCR. Several genes of the âfetal gene programâ, i.e. BNP (4.2-fold, all p<0.05) were induced by stretch as well as PE. We also verified the upregulation of known stretch-responsive genes, including HSP70 (20.9x) and c-myc (3.0x). Moreover, we identified genes exclusively induced by stretch, such as the cardioprotective and antihypertrophic cytokine GDF15 (24.8x) and the antihypertrophic factor heme oxygenase 1 (Hmox1, 10.8x; both confirmed on protein level). Of note, neither PE nor endothelin-1 were able to upregulate GDF15 and Hmox1, while angiotensin II significantly induced both genes. Conversely, addition of the AT1 receptor blocker irbesartan markedly blunted stretch-mediated GDF15 and Hmox1 induction, suggesting that the angiotensin II receptor mediates stretch-dependent signals. In conclusion, we report a comprehensive gene expression profile of cardiomyocytes subjected to biomechanical stress in comparison to pharmacologically induced hypertrophy. Our data imply that a stretch-specific gene program exists, that is mediated, at least in part, by angiotensin-II-dependent signalling. Experiment Overall Design: Three conditions were compared with two replicates each. These are: Experiment Overall Design: (1) control, i.e. no treatment; (2) induction by phenylephrine (50 uM); (3) induction by biomechanical stretch (112%/24h)
2008-06-14 | E-GEOD-5996 | biostudies-arrayexpress
Project description:Neonatal rat ventricular cardiomyocytes (NRVCMs) were stretched biaxially (112%/24h) or stimulated with phenylephrine (PE, 50 uM), both resulting in a similar degree of hypertrophy. Unstretched NRVCMs served as negative control. Affymetrix microarray analysis revealed 164 genes more than 2.0-fold up- and 21 genes less than 0.5-fold downregulated (p<0.01). Differential expression was confirmed by real-time PCR. Several genes of the “fetal gene program”, i.e. BNP (4.2-fold, all p<0.05) were induced by stretch as well as PE. We also verified the upregulation of known stretch-responsive genes, including HSP70 (20.9x) and c-myc (3.0x). Moreover, we identified genes exclusively induced by stretch, such as the cardioprotective and antihypertrophic cytokine GDF15 (24.8x) and the antihypertrophic factor heme oxygenase 1 (Hmox1, 10.8x; both confirmed on protein level). Of note, neither PE nor endothelin-1 were able to upregulate GDF15 and Hmox1, while angiotensin II significantly induced both genes. Conversely, addition of the AT1 receptor blocker irbesartan markedly blunted stretch-mediated GDF15 and Hmox1 induction, suggesting that the angiotensin II receptor mediates stretch-dependent signals. In conclusion, we report a comprehensive gene expression profile of cardiomyocytes subjected to biomechanical stress in comparison to pharmacologically induced hypertrophy. Our data imply that a stretch-specific gene program exists, that is mediated, at least in part, by angiotensin-II-dependent signalling. Keywords: stress response
2007-12-01 | GSE5996 | GEO
Project description:We report different roles of three PRC2 components, KMT6, P55 and SIN3 played in distribution of genome-wide H3K27 tri-methylation of Pyricularia oryzae. Polycomb repressive complex 2 (PRC2), which is composed of Ezh(Kmt6), Su(z)12, Esc(Eed) and accessory subunits RbAp48/Nurf55(P55), catalyzes the methylation of histone H3 at lysine 27. Loss of P55 caused severe global defects in the normal distribution of H3K27me3 and transcriptional reprogramming on the H3K27me3-occupied genes. Furthermore, we found that the Sin3 histone deacetylase complex was required to sustain H3K27me3 occupancy and stably maintain gene repression by directly interacting with P55.
2022-02-20 | GSE195863 | GEO
Project description:To systematically understand how the circadian clock and the nutrient-driven rhythm integrate to regulate SREBP1 activity, we evaluated genome-wide the binding of SREBP1 to its targets along the day in wild-type (WT) C57BL/6mice. The recruitment of SREBP1 to the DNA showed a highly circadian behaviour, with a maximum during the fed status. However, the temporal expression of SREBP1 targets was not always synchronized with its binding. In particular, a different phase of expression was observed for SREBP1 target genes depending on their function, suggesting the involvement of other transcription factors in their regulation. The proper temporal expression pattern of these genes was dramatically changed in Bmal1KO mice upon time-restricted feeding, in spite of the rhythmic, although slightly delayed, binding of SREBP1. Our results show that besides the nutrient-driven regulation of SREBP1 nuclear translocation, a second layer of modulation of SREBP1 transcriptional activity exists and is strongly dependent from the circadian core clock. This system allows to fine tune the expression timing of SREBP1 target genes, thus helping to temporally separate the different physiological processes in which these genes are involved. 6 samples examined, 6 SREBP1 samples, as well as 6 Polr2b and 6 input samples from GEO series GSE35788 CycliX Consortium was a contributor to this submission.
2014-03-10 | E-GEOD-48375 | biostudies-arrayexpress
Project description:To systematically understand how the circadian clock and the nutrient-driven rhythm integrate to regulate SREBP1 activity, we evaluated genome-wide the binding of SREBP1 to its targets along the day in wild-type (WT) C57BL/6mice. The recruitment of SREBP1 to the DNA showed a highly circadian behaviour, with a maximum during the fed status. However, the temporal expression of SREBP1 targets was not always synchronized with its binding. In particular, a different phase of expression was observed for SREBP1 target genes depending on their function, suggesting the involvement of other transcription factors in their regulation. The proper temporal expression pattern of these genes was dramatically changed in Bmal1KO mice upon time-restricted feeding, in spite of the rhythmic, although slightly delayed, binding of SREBP1. Our results show that besides the nutrient-driven regulation of SREBP1 nuclear translocation, a second layer of modulation of SREBP1 transcriptional activity exists and is strongly dependent from the circadian core clock. This system allows to fine tune the expression timing of SREBP1 target genes, thus helping to temporally separate the different physiological processes in which these genes are involved.
2014-03-10 | GSE48375 | GEO
Project description:Anaemia is a frequent complication of chronic infectious diseases but the exact mechanisms by which it develops remain to be clarified. In the present work, we used a mouse model of mycobacterial infection to study molecular alterations of iron metabolism. We show that four weeks after infection with Mycobacterium avium BALB/c mice exhibit a moderate anaemia, which cannot be explained by elevated hepatic hepcidin mRNA expression. Instead, the mice respond with increased mRNA expression of ferroportin (Slc40a1), ceruloplasmin (Cp), hemopexin (Hpx), heme-oxygenase-1 (Hmox1) and lipocalin-2 (Lcn2). Both the anemia and the mRNA expression changes of iron-related genes are largely absent in C.D2 mice which bear a functional allele of the Nramp1 gene. These data suggest that anaemia due to a chronic infection with M. avium develops independently of elevated hepcidin expression and possibly involves ferroportin and/or lipocalin-2. A pool of five mice total RNAs for each condition was used in the experiments. Each two channel chip experiment was done in duplicates with swapped dyes.
2011-07-31 | E-GEOD-20024 | biostudies-arrayexpress
Project description:Background: Clinical data identified an association between the use of HMG-CoA reductase inhibitors (statins) and incident diabetes in patients with underlying diabetes risk factors such as obesity, hypertension and dyslipidemia. The molecular mechanisms however are unknown. Methods: An observational cross-sectional study included 910 severely obese patients, mean (SD) body mass index 46.7 (8.7), treated with or without statins (ABOS cohort: a biological atlas of severe obesity). Data and sample collection took place in France between 2006 and 2016. Transcriptomic signatures of statin treatment in human liver obtained from genome-wide transcriptomic profiling of five different statin drugs using microarrays were correlated to clinico-biological phenotypes and also assigned to biological pathways and mechanisms. Results: We determined the hepatic, statin-related gene signature from genome-wide transcriptomic profiling in severely obese patients with varying degrees of glucose tolerance and cardio-metabolic comorbidities. Patients on statin treatment showed higher diabetes prevalence (OR=2.67; 95%CI, 1.60-4.45; P= 0.0002) and impairment of glucose homeostasis. This phenotype was associated with molecular signatures of increased hepatic de novo lipogenesis (DNL) via activation of sterol regulatory element-binding protein-1 (SREBP1) and concomitant upregulation of the expression of key genes in both fatty acid and triglyceride metabolism. Conclusions: DNL gene activation profile in response to statins was associated with insulin resistance and the diabetic status of the patients. Identified molecular signatures thus suggest that statin treatment increases the risk for diabetes in humans at least in part via induction of DNL.
2019-05-15 | GSE130991 | GEO
Project description:To identify genes regulated by Srebp1 and c-Myc during reprogramming, we performed genome-wide transcriptome profiling in mouse embryonic fibroblasts infected with SKO, SKOM or SKOM plus Srebp1.
2014-11-29 | GSE63705 | GEO