Project description:Transcriptional profiling of left ventricular tissues of Dahl rat with or without treatment of chaetocin Three-condition experiment, Control vs. failing heart, failing heart vs. treatment with chaetocin. 3 samples mixture per each group
Project description:To investigate the effect of calcipotriol treatment, chaetocin treatment and VDR knockdown on gene expression primary normal human fibroblasts, we treated BJ cells with 100 nM calcipotriol for 4 or 24 hours, 50 nM chaetocin for 24 hours, knocked down VDR with si RNA respectively. Then, we performed RNA-seq analysis.
Project description:We recently used a genome-wide screen to demonstrate that numr-1/2 is activated by disruption of RNA metabolism. To investigate numr-1/2 regulation and identify modulators of nucleic acid metabolism, we screened over 40,000 compounds and extracts from commercial and natural product libraries for numr-1/2p::GFP activation. Fungal toxin chaetocin was the most potent and least toxic numr-1/2 inducer. RT-qPCR demonstrates that chaetocin induces numr-1/2 and another stress-responsive SR-like protein gene (W03G1.5) in C. elegans over 50-fold within 45 minutes without affecting expression of canonical heat shock, osmotic stress, endoplasmic reticulum stress, mitochondrial stress, or detoxification response genes. Chaetocin does not activate other metal-responsive genes and actually reduces expression of metallothionein gene mtl-2 and fluorescence of mtl-2p::GFP consistent with repression of mtl-2 transcription. Along with a similar HMTase inhibitor from the same fungal origin - Chetomin, and two synthetic S-methyl-products of Chaetocin and Chetomin, respectively, we tested the expression profile at 5h and 12h post treatment at 500 nM concentration in HCT116 colorectal carcinoma cell line. Both S-methyl-products showed no significant activity or any detectable statistically significant changes in expression compared to the vehicle control. The parent compounds induced a number of expression changes consistent with effects on the stress-response genes in HCT116 cells.
Project description:Chaetocin treatment significantly modulated expression profile of GBM cells such that 373 genes were up and 478 genes were down regulated significantly (FDR<0.05). Genes involved in DNA damage response, reactive oxygen species pathway and cell cycle regulation as well as epithelial to mesenchymal transition are significantly modified by Chaetocin, which render GBM cells much more prone to apoptosis.
Project description:To investigate Chaetocin impact on Diffuse intrinsic pontine gliomas treatment We then performed gene expression profiling analysis using data obtained from RNA-seq of Chaetocin treatment and SUV39H1 knockdown in SU-DIPG36 cells
Project description:Epigenetic status has been linked to cardiac hypertrophy and heart failure. Histone deacetylase inhibitors are promising drugs for preventing cardiac remodeling. We previously demonstrated very different patterns of histone H3 lysine 9 trimethylation (H3K9me3) and histone H3 lysine 4 trimethylation (H3K4me3) in failing hearts compared to control hearts in both animal models and clinical heart specimens. Here, we focused on a heart failure-specific histone modification, H3K9me3, and investigated the prognostic efficacy of administering a histone H3K9 methyltransferase inhibitor, chaetocin, to Dahl salt-sensitive rats, an animal model of heart failure. Chaetocin delayed the timing of transition from cardiac hypertrophy to heart failure, and prolonged survival in this animal model. Mitochondrial dysfunction was improved with inhibitor use in the failing heart. ChIP-seq analysis demonstrated that heart failure caused an increase in H3K9me3 alignments in thousands of repetitive elements, including regions neighboring mitochondrial genes, and a corresponding reduction of this effect with inhibitor use. However, at 35 loci, heart failure was conversely associated with a reduction in H3K9me3 alignments, and inhibitor use reversed this effect. These data suggest that excessive heterochromatinization of repetitive elements in the failing heart might impair pumping function with mitochondrial gene silencing. H3K9 methyltransferase inhibitors may be a promising novel therapy for chronic heart failure.
