Histone H3 T11 phosphorylation by Sch9 and CK2 regulates lifespan by controlling the nutritional stress response [ChIP-seq]
ABSTRACT: We report the changes of Histone H3 T11 phosphorylation (H3pT11) signal upon nutritional stress (YP with 3% glycerol). Overall design: Two replicates each of H3pT11 ChIP in YPD (YP media with 2% glucose) and YPglycerol (YP with 3% glycerol) as well as corresponding H3 IP samples (used as controls).
Upon nutritional stress, the metabolic status of cells is changed by nutrient signaling pathways to ensure survival. Altered metabolism by nutrient signaling pathways has been suggested to influence cellular lifespan. However, it remains unclear how chromatin regulation is involved in this process. Here, we found that histone H3 threonine 11 phosphorylation (H3pT11) functions as a marker for nutritional stress and aging. Sch9 and CK2 kinases cooperatively regulate H3pT11 under stress conditions. ...[more]
Project description:We report mRNA expression changes upon nutritional stress condition in WT strains and Histone H3T11 phosphorylation defective mutants. Overall design: Three replicates each comparing RNA expression levels between wild type, cka1 mutant in various stress conditions.
Project description:The following CGH experiments were conducted on six sectors (S1-S6) from a single primary ductal carcinoma tumor (T11) using the Sector-Ploidy-Profiling (SPP) Approach. SPP involves macro-dissecting the tumor, flow-sorting nuclei by differences in total genomic DNA content and profiling the genome of the tumor subpopulations. Overall design: The genomic DNA from each tumor subpopulation was labeled with Cy5 and hybridized to an 85K Bgl2 ROMA Microarray. A normal reference male fibroblast was labeled with Cy3 as a control. Samples were dye-swapped and the experiments were conducted in color-reversal. The value data repesents a log ratio of the mean of two dye-swapped samples
Project description:Conjugated Linoleic Acid (CLA) is a collective term for the positional and geometric isomers of linoleic acid. In recent years CLA has been reported to have anti-carcinogenic, anti-obesity, anti-inflammatory and anti-artherogenic effects. The aim of this study was to determine the effects of a natural high-CLA enriched beef source on three primary insulin responsive tissues: adipose, liver and skeletal muscle. ob/ob mice were assigned to one of two diets: a control beef diet, low in c9, t11-CLA (control diet) or a c9, t11-CLA enriched beef diet. After a 28 day feeding trial, RNA was extracted from adipose, liver and skeletal muscle tissue and hybridized to Affymetrix microarrays.
Project description:Conjugated Linoleic Acid (CLA) is a collective term for the positional and geometric isomers of linoleic acid. In recent years CLA has been reported to have anti-carcinogenic, anti-obesity, anti-inflammatory and anti-artherogenic effects. The aim of this study was to determine the effects of a natural high-CLA enriched beef source on three primary insulin responsive tissues: adipose, liver and skeletal muscle. Overall design: ob/ob mice were assigned to one of two diets: a control beef diet, low in c9, t11-CLA (control diet) or a c9, t11-CLA enriched beef diet. After a 28 day feeding trial, RNA was extracted from adipose, liver and skeletal muscle tissue and hybridized to Affymetrix microarrays.
Project description:Saccharomyces cerevisiae Mek1 is a CHK2/Rad53-family kinase that regulates meiotic recombination and progression upon its activation in response to DNA double-strand breaks (DSBs). The full catalog of direct Mek1 phosphorylation targets remains unknown. Here, we show that phosphorylation of histone H3 on threonine 11 (H3 T11ph) is induced by meiotic DSBs in S. cerevisiae and Schizosaccharomyces pombe. Molecular genetic experiments in S. cerevisiae confirmed that Mek1 is required for H3 T11ph and revealed that phosphorylation is rapidly reversed when Mek1 kinase is no longer active. Reconstituting histone phosphorylation in vitro with recombinant proteins demonstrated that Mek1 directly catalyzes H3 T11 phosphorylation. Mutating H3 T11 to nonphosphorylatable residues conferred no detectable meiotic defects, indicating that H3 T11ph is dispensable for Mek1 functions in controlling recombination. However, H3 T11ph provides an excellent marker of ongoing Mek1 kinase activity in vivo. Anti-H3 T11ph chromatin immunoprecipitation followed by deep sequencing demonstrated that H3 T11ph was highly enriched at presumed sites of attachment of chromatin to chromosome axes, gave a more modest signal along chromatin loops, and was present at still lower levels immediately adjacent to DSB hotspots. These localization patterns closely tracked the distribution of Red1 and Hop1, axis proteins required for Mek1 activation. These findings provide insight into the spatial disposition of Mek1 kinase activity and the higher order organization of recombining meiotic chromosomes. Overall design: ChIP-seq analysis of Red1 on budding yeast meiotic chromosomes Distribution of Red1 at 3h after meiotic induction
Project description:T11 Target structure (T11TS), a membrane glycoprotein isolated from sheep erythrocytes, reverses the immune suppressed state of brain tumor induced animals by boosting the functional status of the immune cells. This study aims at aiding in the design of more efficacious brain tumor therapies with T11 target structure. We propose a mathematical model for brain tumor (glioma) and the immune system interactions, which aims in designing efficacious brain tumor therapy. The model encompasses considerations of the interactive dynamics of glioma cells, macrophages, cytotoxic T-lymphocytes (CD8(+) T-cells), TGF-β, IFN-γ and the T11TS. The system undergoes sensitivity analysis, that determines which state variables are sensitive to the given parameters and the parameters are estimated from the published data. Computer simulations were used for model verification and validation, which highlight the importance of T11 target structure in brain tumor therapy.
Project description:Many studies have addressed the effect of dietary glycemic index on obesity and diabetes, but little is known about its effect on lifespan itself. We found that adding a small amount of glucose to the medium (0.1-2%) shortened the lifespan of C. elegans. Glucose shortened lifespan by inhibiting the activities of lifespan-extending transcription factors that are also inhibited by insulin signaling: the FOXO family member DAF-16 and the heat shock factor HSF-1. This effect involved the down-regulation of an aquaporin glycerol channel, aqp-1. We show that changes in glycerol metabolism are likely to underlie the lifespan-shortening effect of glucose, and that aqp-1 may act cell non-autonomously as a feedback regulator in the insulin/IGF-1 signaling pathway. Insulin down-regulates similar glycerol channels in mammals, suggesting that this glucose-responsive pathway might be conserved evolutionarily. Together these findings raise the possibility that a low-sugar diet might have beneficial effects on lifespan in higher organisms. Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE18561: Adult C. elegans: Control daf-2 mutants treated with daf-16 RNAi vs. daf-2 mutants treated with empty vector RNAi GSE18562: Adult C. elegans: Control OP50 culture vs. OP50 + 2% glucose culture
Project description:A Trichoderma microarrays composed of 385,000 probes, designed against the genomes of Trichoderma reesei (= Hypocrea jecorina), ID: 431241 (9,129 genes) + Trichoderma virens (= Hypocrea virens), ID: 413071 (11,643 genes) + Trichoderma atroviride (= Hypocrea atroviridis) ID: 197014A (11,643 genes), was constructed (Roche-NimbleGen, Inc., Madison, WI, USA). Probes contained entere transcript sequence. This microarray was used to analyze the transcriptomic changes of T. atroviride IMI 352941 (T11) in three conditions: T11 growing alone, T11 growing at ca 5 mm of V. dahliae V-138I and T11 overgrowing V-138I. Overall design: Three samples were analyzed as follows: T. atroviride IMI 352941 (T11) grown alone (SOM05CVT), used as control, T11 grown at ca. 5 mm of V. dahliae V-138I (SOM05CVV) and T11 overgrowing V-138I (SOM05CVW). Three replicates for each sample were performed.