Genome-wide profiling of Ixr1 binding to the chromatin in Saccharomyces cerevisiae and the changes associated to cisplatin treatment.. Saccharomyces cerevisiae

Ixr1 is a Saccharomyces cerevisiae HMGB protein that regulates the transcription of genes related to the response to changes normoxia-hypoxia, oxidative stress response or in the readaptation of catabolic and anabolic fluxes during oxygen limitation. Besides, Ixr1 binds to cisplatin-DNA adducts with high affinity. It is known that cancerous cells usually acquire resistance against the drug after the initial treatment, thus limiting its effectiveness. Yeast has been used as an easy-handled eukaryotic model to find genes related to cisplatin responsiveness and IXR1 is one among those that increase sensitivity. In this work, transcriptome analyses have been done to understand the regulatory roles of Ixr1 in absence or presence of cisplatin. Ixr1 behaves in yeast as a master regulator of other transcriptional factors, which respond to external stimuli and control cell growth, and proliferation. Diverse approaches including qPCR, ChIP and measure of 18S and 25S rRNAs confirm a function of Ixr1 in the control of ribosome biogenesis. Furthermore, several connections between this control, the TOR signaling pathway and cisplatin resistance in ixr1Δ mutants were found. Overall design: In total 10 arrays: 6 samples (2 different conditions; 3 biological replica) with their corresponding input controls (2 biological replica).