In silico identification of key regulators instigating the pre-meiotic phase during respiration in Saccharomyces...

Like higher eukaryotes, diploid MATa/MATα budding yeasts can undergo both mitosis and meiosis. Although the potential reason for their phase switching is elucidated by two consecutive processes, i.e. transition from fermentation (mitotic growth) to respiration in glucose-deficient media and then complete shift to meiotic phase in combined nitrogen- and glucose-starved media, the genomic interactions and regulatory cascade operating this drive remain elusive. Here, we aim to explore the regulatory cross-talk that mediates the phase transition. We have hypothesized that pre-growth in glucose-starved condition (yeast extract-peptone-acetate media) not only causes switch from fermentation to respiration but also prepares them for meiosis via a myriad of signaling events regulated by transcription factors (TFs). We have identified 23 putative TFs from integrated protein-protein interaction and gene regulatory network that were reconstructed from predicted and experimentally validated data. A total of six TFs (Xbp1p, Abf1p, Cbf1p, Ste12p, Reb1p and Gcn4p) are found to be highly connected in the network and involved in the cross-talk between respiration and cellular preparation for meiosis. We have identified Abf1p and Adr1p as the master regulators of the integrated network. This study in yeast will help to decipher the pre-meiotic initiation that occurs in higher eukaryotes.