Project description:To characterize target specificity of TETi76, we performed global gene expression analyses of K562TET2+/+ and TET2-/- control cells; TETi76 mimicked expression signatures generated by the loss of TET2 in K562. The addition of Ascorbic Acid (AA), known to enhance TET-dioxygenase activity, counteracted the changes induced by TETi76. In order to study the molecular pathway of synthetic lethality by TET-dioxygenase inhibition, natural TET2-/- mutant cell line SIGM5 was treated with TET inhibitor TETi76 and global gene expression analysis was performed by RNAseq. Result demostrate a significant upregulation of TNT-α signaling and the down regulation of Interferon-α signaling. Interestingly, we also observed significant up-modulation of oxidative stress response pathway genes consistent with the inhibition of dioxygenases. In particular, TETi76 treatment induces 8-fold increase of oxidative stress sensor NQO1 a NRF2 target gene that has been shown earlier to induce pro-apoptotic cell death in cancer cells.
Project description:Assessment of synthetic lethality between a temperature-sensitive allele of CDC102 and Yeast Deletion mutations Keywords: repeat sample
Project description:Synthetic lethality is a type of genetic interaction in which two non-lethal mutations acting together result in a loss of viability. Such interactions are important for the insights they may offer into how gene functions are organized into distinct cellular processes. The datasets in this Series represent an effort to identify synthetic lethal genetic interactions in the yeast Saccharomyces cerevisiae on a genome-wide scale. Please see the Pubmed IDs in the individual Sample annotations.