Project description:Cell growth is controlled by nutrients and growth factors. How cells are regulated to enter stationary phase is still poorly understood. Previously we have identified 17 yeast genes whose expression is significantly up-regulated following starvation for different macro-nutrients. Here we demonstrate that activation of some of these genes is dependent on the Rim15 kinase and the Gis1 transcription factor. Phenotypic and microarray analyses reveal that Rim15p and Gis1p have both overlapping and distinct functions suggesting a non-linear relationship between the two. Subsequently we demonstrate that independent of Rim15p, TOR controls the limited proteolysis of Gis1p and regulates the binding of functional fragments to their target promoters. The limited proteolysis of Gis1p is executed by the proteasome to prevent its target genes from over activation. Thus, TOR regulates the function of the proteasome in response to nutrients so that gene expression is properly controlled, not only during active growth, but also in stationary phase.
Project description:Transcript profiles of Laccaria bicolor S238N mycelium on various media were analyzed. The array probes were designed from gene models taken from the Joint Genome Institute (JGI, department of energy) Laccaria bicolor genome sequence version 1. One goal was to evaluate the effect of nutrient deprivation on the transcriptome of Laccaria bicolor. We performed 15 hybridizations (Roche-NimbleGen) with samples derived from Laccaria bicolor free-living mycelium grown on MMN medium, on MMN with a 10 times reduction in all major macro-elements, on MMN with a 10 times reduction in the quantity of glucose or onto agar medium supplemented with the same nutrients used to fertilize our mycorrhization experiments.
Project description:Background & Aims: The contribution of genetics to the pathogenesis of inflammatory bowel disease (IBD) has been established by twin studies, targeted sequencing and genome-wide association studies (GWASs). This has yielded a plethora of risk loci with an aim to identify causal variants. Research on the genetic components of IBD has mainly focused on protein coding genes, thereby omitting other functional elements in the human genome i.e. the regulatory regions. Methods: Using acetylated histone 3 lysine 27 (H3K27ac) chromatin immunoprecipitation and sequencing (ChIP-seq), we identified tens of thousands of potential regulatory regions that are active in intestinal epithelium and immune cells, the main cell types involved in IBD. We correlated these regions with susceptibility loci for IBD. Results: We show that 45 out of 163 single nucleotide polymorphisms (SNPs) associated with IBD co-localize with active regulatory elements. In addition, another 47 IBD associated SNPs co-localize with active regulatory element via other SNP in strong linkage disequilibrium. Altogether 92 out of 163 IBD-associated SNPs can be connected with distinct regulatory element. This is 2.5 to 3.5 times more frequent than expected from random sampling. The genomic variation in these SNPs often creates or disrupts known binding motifs - thereby possibly affecting the binding affinity of transcriptional regulators and altering the expression of regulated genes. Conclusions: We show that in addition to protein coding genes, non-coding DNA regulatory regions, active in immune cells and in intestinal epithelium, are involved in IBD. H3K27ac ChIP-seq (ab4729, Abcam) profile of 7 intestinal epithelial samples
Project description:Imprinted macro ncRNAs such as Airn play an important role in silencing protein-coding genes in cis, macro ncRNAs could be a common feature in all imprinted gene clusters. By applying the RNA Expression on Tiling Array (RETA) technique, macro ncRNAs were found to be abundant in 26 known mouse genomic regions containing imprinted genes were detected. All well-known imprinted macro ncRNAs were up-regulated upon depletion of DNA methylation.
Project description:The early detection of tissue and organ damage associated with autoimmune diseases (AID) has been identified as key to improve long-term survival, but non-invasive biomarkers are lacking. Elevated cell-free DNA (cfDNA) levels have been observed in AID and inflammatory bowel disease (IBD), prompting interest to use cfDNA as a potential non-invasive diagnostic and prognostic biomarker. Despite these known disease-related changes in concentration, it remains impossible to identify AID and IBD patients through cfDNA analysis alone. By using unsupervised clustering on large sets of shallow whole-genome sequencing (sWGS) cfDNA data, we uncover AID- and IBD-specific genome-wide patterns in plasma cfDNA in both the obstetric and general AID and IBD populations. Supervised learning of the genome-wide patterns allows AID prediction with 50% sensitivity at 95% specificity. Importantly, the method can identify pregnant women with AID during routine non-invasive prenatal screening. Since AID pregnancies have an increased risk of severe complications, early recognition or detection of new onset AID can redirect pregnancy management and limit potential adverse events. This method opens up new avenues for screening, diagnosis and monitoring of AID and IBD.
Project description:Here we describe our unprecedented approach in proposing parsley (PAR) as a nutraceutical intervention in inflammatory bowel disease (IBD) using a mouse model of dextran sodium sulphate (DSS)-induced colitis, following a multi-integrated-omics analysis. PAR supplementation (n=7) significantly improved colon shortening and increased the disease activity index compared to the DSS group (n=7). The colonic transcriptome revealed the down-regulation of inflammatory cytokines, and the hepatic transcriptome and metabolome revealed the up-regulation of fatty acid synthesis genes, thereby improving body weight loss. Down-regulated cancer markers were observed in the hepatic transcriptome and proteome. A global plasma metabolite analysis indicated shifts in the citric cycle and urea cycle, implicating improved impaired glycolysis and oxidative stress. Our integration of three omics analyses highlighted the involvement of the methionine-recycling pathway and PAR’s role in decreasing the risk of IBD. This pioneering use of multi-integrated-omics in the evaluation of nutrients’ effects on physiology is expected to be widely useful and informative, shaping the future of nutritional research. Here we describe our unprecedented approach in proposing parsley (PAR) as a nutraceutical intervention in inflammatory bowel disease (IBD) using a mouse model of dextran sodium sulphate (DSS)-induced colitis, following a multi-integrated-omics analysis. PAR supplementation (n=7) significantly improved colon shortening and increased the disease activity index compared to the DSS group (n=7). The colonic transcriptome revealed the down-regulation of inflammatory cytokines, and the hepatic transcriptome and metabolome revealed the up-regulation of fatty acid synthesis genes, thereby improving body weight loss. Down-regulated cancer markers were observed in the hepatic transcriptome and proteome. A global plasma metabolite analysis indicated shifts in the citric cycle and urea cycle, implicating improved impaired glycolysis and oxidative stress. Our integration of three omics analyses highlighted the involvement of the methionine-recycling pathway and PAR’s role in decreasing the risk of IBD. This pioneering use of multi-integrated-omics in the evaluation of nutrients’ effects on physiology is expected to be widely useful and informative, shaping the future of nutritional research.
Project description:The response of critical microbial taxa to litter micro-nutrients and macro-chemistry determined the agricultural soil priming intensity after afforestation
| PRJNA758440 | ENA
Project description:Military dog macro genome project