ABSTRACT

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.

中文翻译：

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计算机识别在酿酒酵母呼吸过程中启动减数分裂前阶段的关键调节因子

摘要

与高等真核生物一样，二倍体 MATa/MATα 芽殖酵母可以进行有丝分裂和减数分裂。尽管通过两个连续过程阐明了它们的相转换的潜在原因，即在葡萄糖缺乏培养基中从发酵（有丝分裂生长）过渡到呼吸，然后在氮和葡萄糖缺乏的联合培养基中完全转变为减数分裂期，但基因组相互作用运行这种驱动器的监管级联仍然难以捉摸。在这里，我们旨在探索调节相变的监管串扰。我们假设葡萄糖缺乏条件下的预生长（酵母提取物-蛋白胨-乙酸酯培养基）不仅会导致从发酵转变为呼吸，而且还通过转录因子 (TF) 调控的无数信号事件为减数分裂做好准备。我们已经从整合的蛋白质 - 蛋白质相互作用和基因调控网络中确定了 23 个推定的 TF，这些网络是根据预测和实验验证的数据重建的。发现共有六个 TF（Xbp1p、Abf1p、Cbf1p、Ste12p、Reb1p 和 Gcn4p）在网络中高度连接，并参与呼吸和细胞减数分裂准备之间的串扰。我们已将 Abf1p 和 Adr1p 确定为集成网络的主要调节器。这项在酵母中的研究将有助于破译高等真核生物中发生的减数分裂前起始。Reb1p 和 Gcn4p) 被发现在网络中高度连接，并参与呼吸和细胞减数分裂准备之间的串扰。我们已将 Abf1p 和 Adr1p 确定为集成网络的主要调节器。这项在酵母中的研究将有助于破译高等真核生物中发生的减数分裂前起始。Reb1p 和 Gcn4p) 被发现在网络中高度连接，并参与呼吸和细胞减数分裂准备之间的串扰。我们已将 Abf1p 和 Adr1p 确定为集成网络的主要调节器。这项在酵母中的研究将有助于破译高等真核生物中发生的减数分裂前起始。