ChIP-seq for Leu3 with addition of different levels of leucine, valine and isoleucine
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ABSTRACT:
PROVIDER: PRJEB36934 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR3957620_1.fastq.gz | Fastqsanger.gz | |||
| ERR3957611_1.fastq.gz | Fastqsanger.gz | |||
| ERR3957612_1.fastq.gz | Fastqsanger.gz | |||
| ERR3957613_1.fastq.gz | Fastqsanger.gz | |||
| ERR3957614_1.fastq.gz | Fastqsanger.gz |
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Project description:In this experiment we wanted to see how the binding behavior of the S. Cerevisiae transcription factor Leu3, on of the main regulators of leucine biosynthesis, is affected by different availability of the branched chain amino acids. For this we grow the cells in shake flask under glucose limitation and treated them 2 hours before sampling. The cells were then cross-linked with formaldehyde and ChIP-seq was performed using the Oxford Nanopore MinIon.
2020-07-01 | E-MTAB-8820 | biostudies-arrayexpress
Project description:Here we report on an RNAseq method in combination with spike-in cells to measure global changes in the transcription pattern after valine-induced isoleucine starvation of a standard E. coli K12 strain. Due to the spike-in method we were able to show that ribosomal RNA is degraded during isoleucine starvation and we showed how this change in cellular RNA content affect the estimated regulation of mRNA levels compared to if spike-in were not utilized. Our analysis also showed that induction of starvation by sudden addition of high valine concentrations provoked prominent regulatory responses outside of the expected ppGpp, RpoS and Lrp regulons
2019-11-19 | GSE136753 | GEO
Project description:Colorectal cancer (CRC) is currently the third in cancer incidence worldwide and the fourth most common cause of cancer deaths. To discover the proteins related to colon cancer, a typical inflammation-related C57B/6N mouse colon carcinogenesis model was developed using azoxymethane-dextran sodium sulfate (AOM-DSS) treated for 14 weeks. iTRAQ-based proteomics study was performed using cell membrane components enriched from colonic mucosa. Tumor tissues and their adjacent normal colon tissues from colonic cancer patients were collected for differential protein detection and metabolomics studies. Totally, 74 differentially expressed proteins were identified in the AOM/DSS treated tumor samples compared with AOM/DSS treated adjacent samples, and the saline treated control. Bioinformatics analysis showed that eight downregulated proteins were enriched in the pathway of valine, leucine and isoleucine degradation. Targeted metabolomics study showed that valine, leucine and isoleucine was upregulated in tumor tissues compared with their adjacent normal tissues from colonic cancer patients. Further real-time PCR and western blot experiments showed that the signal pathway proteins of Hadh and ALDH2 were downregulated in colon patients (colon tumor tissues vs their adjacent colon tissues), as well as in AOM/DSS treated mouse model. In all, our study showed that the pathway of valine, leucine and isoleucine degradation was inactivation in colon cancer, and Hadh and ALDH2 were two potential biomarkers for colon cancer treatment.
2023-11-13 | PXD046882 |
Project description:Abstract: Non-alcoholic steatohepatitis (NASH) is associated with a disturbed metabolism in liver and excessive accumulation of ectopic fat. Branched-chain amino acids (BCAAs) may beneficially modulate hepatic lipids, however it remains unclear whether individual BCAAs can attenuate already established NASH and oxidative-inflammatory stress associated with it. Therefore, mice were first put on a run-in fast food diet (FFD) for 26 weeks, these obese mice were then treated with individual BCAAs valine or isoleucine (3% of FFD) for another 12 weeks and compared to FFD controls. Valine and isoleucine treatment did not affect obesity, dyslipidemia, gut permeability or fecal fatty acid excretion, although significantly reduced hyperinsulinemia compared with FFD. Valine and isoleucine significantly reduced ALT, CK-18M30, and liver steatosis with a particularly pronounced effect on the microvesicular component (-61% by valine and -71% by isoleucine). Hepatic 4-hydroxynonenal (4-HNE) immunoreactivity, a marker for oxidative stress-induced lipid peroxidation, was also significantly decreased. Functional genomics analysis demonstrated that valine and isoleucine upregulated BCAA metabolism, deactivated master regulators of anabolic pathways related to steatosis (e.g. SREBPF1) and activated master regulators of mitochondrial biogenesis (e.g. PPARGC1a) and lipid catabolism (e.g. ACOX1, AMPK). The correction of critical metabolic pathways by valine and isoleucine was accompanied by a significant decrease of liver inflammation, and suppression of many FFD-stimulated cytokine and chemokine pathways including IL-1β, TNFα and CCR2 signaling. In conclusion, the dietary intervention with either valine or isoleucine corrected multiple metabolic processes in liver and reduced steatosis and inflammation with profound effects on oxidative stress and inflammatory pathways. Methods: Putative antifibrotic effects of butyrate were studied in Ldlr-/-.Leiden mice fed an obesogenic NASH-inducing diet (HFD) containing 2.5% (w/w) butyrate for 38 weeks and compared to an HFD control group. Antifibrotic mechanisms of butyrate were further investigated in TGF-β-stimulated primary human hepatic stellate cells (HSC). Results: HFD-fed mice developed obesity, insulin resistance, increased levels of plasma leptin, adipose tissue inflammation, gut permeability, dysbiosis and NASH-associated fibrosis. Butyrate corrected hyperinsulinemia, lowered plasma leptin levels and attenuated adipose tissue inflammation, without affecting gut permeability or microbiota composition. Butyrate lowered plasma ALT and CK-18M30 and attenuated hepatic steatosis and inflammation. Butyrate inhibited fibrosis development as demonstrated by decreased hepatic collagen content and Sirius-red-positive area. In TGF-β-stimulated HSC, butyrate dose-dependently reduced collagen deposition and decreased procollagen1α1 and PAI-1 protein expression. Transcriptomic analysis and subsequent pathway and upstream regulator analysis revealed deactivation of specific non-canonical TGF-β signaling pathways RhoA/Rock and PI3K/AKT and other important pro-fibrotic regulators (e.g. YAP/TAZ and MYC) by butyrate, providing a potential rationale for its antifibrotic effects. Conclusions: Butyrate protects against the development of obesity and insulin resistance-associated NASH and liver fibrosis. These antifibrotic effects are at least in part attributable to a direct effect on collagen production in hepatic stellate cells, as a result of inhibiting non-canonical TGF-β signaling.
2022-06-30 | GSE195798 | GEO
Project description:For the first time in Lactococcus lactis, amino acid starvation response was characterized. The natural imposition of isoleucine starvation, by its consumption during growth, associated to transcript profiling, allowed defining exhaustively this stress stimulon. It consisted of a general induction of nitrogen metabolism (amino acid biosynthesis and transport, proteolytic system and proteases), a strong repression of genes encoding major physiological activities (translation, transcription, carbon metabolism, purine and pyrimidine biosynthesis and fatty acid metabolism) and the induction of unexpected cross responses to acid, osmotic and oxidative stresses. Keywords: stress response, time course Isoleucine starvation was imposed by the consumption of this amino acid during the growth of Lactococcus lactis IL1403 on ILV0.1 medium (CDM with ten-fold reduced concentrations of isoleucine, leucine and valine) and under controlled conditions (30 °C, pH 6.6, nitrogen atmosphere). Cell samples were harvested in exponential phase and after 30 min, 1.7 h and 3.5 h of isoleucine starvation. Total RNA was extracted from these samples and radiolabelled cDNA were prepared and hybridized on nylon arrays. 2053 amplicons specific of Lactococcus lactis IL1403 genes were spotted twice on the array. The 4 time-points were analyzed simultaneously and 3 independent repetitions were performed.
2010-06-25 | E-GEOD-4872 | biostudies-arrayexpress
Project description:Background Cells regulate protein synthesis in response to fluctuating nutrient availability through mechanisms that affect both translation initiation and elongation. Branched-chain amino acids, leucine, isoleucine, and valine, are essential nutrients. However, how their depletion affects translation remains largely unclear. Here, we investigate the immediate effects of single, double, and triple branched-chain amino acid deprivation on translational dynamics in NIH3T3 cells using RNA-seq and ribosome profiling. Results All starvation conditions increased ribosome dwell times, with pronounced stalling at all valine codons during valine and triple starvation, whereas leucine and isoleucine starvation produced milder, codon-specific effects. Notably, stalling under isoleucine deprivation largely decreased under triple starvation. Positional enrichment of valine codons near the 5′ end and downstream isoleucine codons potentially contributes to these patterns, suggesting a possible elongation bottleneck that influences translational responses under branched-chain amino acid starvation. The presence of multiple valine stalling sites was associated with decreased protein levels. Finally, codon-specific dwell time changes correlated strongly with patterns of tRNA isoacceptor charging. Conclusions Together, these findings suggest that differential ribosome stalling under branched-chain amino acid starvation reflects a balance between amino acid supply, tRNA charging dynamics, codon position, and stress-response signaling.
2025-09-02 | GSE291653 | GEO
Project description:Background: Cells regulate protein synthesis in response to fluctuating nutrient availability through mechanisms that affect both translation initiation and elongation. Branched-chain amino acids, leucine, isoleucine, and valine, are essential nutrients. However, how their depletion affects translation remains largely unclear. Here, we investigate the immediate effects of single, double, and triple branched-chain amino acid deprivation on translational dynamics in NIH3T3 cells using RNA-seq and ribosome profiling. Results: All starvation conditions increased ribosome dwell times, with pronounced stalling at all valine codons during valine and triple starvation, whereas leucine and isoleucine starvation produced milder, codon-specific effects. Notably, stalling under isoleucine deprivation largely decreased under triple starvation. Positional enrichment of valine codons near the 5' end and downstream isoleucine codons potentially contributes to these patterns, suggesting a possible elongation bottleneck that influences translational responses under branched-chain amino acid starvation. The presence of multiple valine stalling sites was associated with decreased protein levels. Finally, codon-specific dwell time changes correlated strongly with patterns of tRNA isoacceptor charging. Conclusions: Together, these findings suggest that differential ribosome stalling under branched-chain amino acid starvation reflects a balance between amino acid supply, tRNA charging dynamics, codon position, and stress-response signaling.
2025-09-02 | GSE291652 | GEO
Project description:Cholesterol performs multiple essential roles in cells. Enhanced cholesterol synthesis and storage in lipid droplets have been linked to cancer aggressiveness, particularly in lipid-rich and hormone-sensitive cancers such as prostate cancer . Cholesterol anabolism and catabolism are finely regulated in tumor cells in response to various nutritional states. Mitochondria have increasingly been recognized as a signal transduction organelle, particularly concerning metabolites derived from mitochondrial activity. The link between mitochondrial regulation and cholesterol synthesis remains inadequately understood. Here, we show that propionyl-CoA promotes cholesterol synthesis, storage, and further progression in prostate cancer cells. We found that propionyl-CoA, mainly produced by isoleucine and valine metabolism in the mitochondria, can translocate through the mitochondrial membrane and serves as a substrate for modifying cleaved SREBP2, stabilizing it and thereby promoting cholesterol synthesis and storage in lipid droplets. This process facilitates cancer metastasis and castration resistant partially through enhancing androgen synthesis in prostate cancer cells. Our results demonstrate that branched-chain amino acid (BCAA) catabolism and propionate metabolism in mitochondria are involved in the regulation of cholesterol synthesis and utilization through metabolite-mediated protein modification. We anticipate that our findings provide a critical link between amino acid metabolism and cholesterol anabolism, highlighting a mechanism that plays a crucial role in the development of castration resistance in prostate cancer patients. This study offers a theoretical rationale for targeting the production of propionyl-CoA, particularly through the metabolism of isoleucine and valine, as an effective strategy to inhibit cholesterol synthesis and its related diseases.
2025-07-11 | GSE272086 | GEO
Project description:Four experiments were conducted to estimate the optimal standardized ileal digestible (SID) level of branched-chain amino acids in low-protein diets during the starter, grower, and finisher periods, using the response surface methodology, and to study their effects on performance and mRNA expression of genes involved in the mechanistic target of rapamycin (mTOR) pathway of broiler chickens from 8 to 21 D of age. In experiments 1, 2, and 3, a total of 1,500 Cobb male broiler chickens were assigned to 15 diets of a central composite rotatable design (CCD) of response surface methodology containing 5 levels of SID Leu, Val, and Ile with 5 replicate pens of 20 birds each. A 3-factor, 5-level CCD platform was used to fit the second-order polynomial equation of broiler performance. In experiment 4, a total of 540 8-day-old Cobb male broiler chickens were distributed in a completely randomized 2 x 3 x 3 factorial arrangement with 2 SID Leu levels (1.28 or 1.83%), 3 SID Val levels (0.65, 0.90, or 1.20%), and 3 SID Ile levels (0.54, 0.79, or 1.09%) for a total of 18 treatments with 5 replicate cages of 6 birds each. High Leu levels impaired (P < 0.05) gain:feed when birds were fed marginal Val or Ile diets. However, gain:feed was restored when both Val and Ile were supplemented to reach adequate or high levels. High Leu levels increased (P < 0.05) mRNA expression of S6K1 and eEF2 genes only in birds fed high Ile levels. Dietary SID Leu, Val, and Ile levels required for gain:feed optimization in low-protein diets were estimated at 1.37, 0.94, and 0.87% during the starter period; 1.23, 0.82, and 0.75% during the grower period; and 1.15, 0.77, and 0.70% during the finisher phase, respectively. Higher Val and Ile levels are required to optimize the effect of Leu supplementation on mRNA expression of mTOR pathway genes in the pectoralis major muscle of broilers from day 1 to 21 after hatch.
| S-EPMC7647919 | biostudies-literature
Project description:Dietary protein is a critical regulator of metabolic health and aging in diverse species, and many of the benefits of low-protein diets are recapitulated by restriction of the three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine. In mouse models of Alzheimer’s disease (AD), dietary supplementation with BCAAs worsens AD neuropathology, while restriction of any of the BCAAs improves cognitive deficits. We recently discovered that each BCAA has distinct metabolic effects, with the restriction of isoleucine alone being sufficient to improve metabolic health and extend lifespan and healthspan in genetically diverse mice. Here, we investigate the effect of restricting each individual BCAA on metabolic health and the development and progression of AD in the 3xTg mouse model. We find that restriction of isoleucine and valine, but not leucine, promotes metabolic health. Restricting any of the three BCAAs improved short-term memory in males, with isoleucine restriction having the strongest effect, while restricting valine has the greatest cognitive benefits in females. Restriction of each BCAA had distinct effects on AD pathology, mTOR signaling, autophagy, and survival. Transcriptomic analysis of the brain revealed both distinct and shared, and highly sex-specific, molecular impacts of restricting each BCAA, and we identify a set of significantly altered pathways strongly associated with reduced AD pathology and improved cognitive performance in males. Our findings suggest that restricting any of the BCAAs, particularly isoleucine or valine, may form the basis of a novel sex-specific approach to prevent or delay the progression of AD.
2025-07-30 | GSE299928 | GEO