INO80 Chromatin Remodelling Coordinates Metabolic Homeostasis with Cell Division

Adaptive survival requires the coordination of nutrient availability with expenditure of cellular resources. For example, in nutrient-limited environments, 50% of all S. cerevisiae genes synchronize and exhibit periodic bursts of expression in coordination with respiration and cell division in the Yeast Metabolic Cycle (YMC). Despite the importance of metabolic and proliferative synchrony, the majority of YMC regulators are currently unknown. Here we demonstrate that the INO80 chromatin-remodelling complex is required to coordinate respiration and cell division with periodic gene expression. Specifically, INO80 mutants have severe defects in oxygen consumption and promiscuous cell division that is no longer coupled with metabolic status. In mutant cells, chromatin accessibility of periodic genes, including TORC-responsive genes, is relatively static, concomitant with severely attenuated gene expression. Collectively, these results reveal that the INO80 complex mediates metabolic signaling to chromatin in order to restrict proliferation to metabolically optimal states.

适应性生存需要营养物质的可利用性与细胞资源的消耗相协调。例如，在营养受限的环境中，所有酿酒酵母基因中有50%会同步，并在酵母代谢周期（YMC）中与呼吸作用和细胞分裂协同表现出周期性的表达爆发。尽管代谢和增殖同步性很重要，但目前大多数YMC调节因子尚不清楚。在此我们证明，INO80染色质重塑复合物是使呼吸作用和细胞分裂与周期性基因表达相协调所必需的。具体而言，INO80突变体在耗氧量方面存在严重缺陷，细胞分裂紊乱，不再与代谢状态相耦合。在突变细胞中，周期性基因（包括TORC响应基因）的染色质可及性相对静止，同时基因表达严重减弱。总之，这些结果表明INO80复合物介导代谢信号传递至染色质，以便将增殖限制在代谢最佳状态。