PDF(Pubmed)
Abstract：
Cellular quiescence is an important physiological state both in unicellular and multicellular eukaryotes. Quiescent cells are halted for proliferation and stop the cell cycle at the G0 stage. Using fission yeast as a model organism, we have previously found that several subunits of a conserved chromatin remodeling complex, Ino80C (INOsitol requiring nucleosome remodeling factor), are required for survival in quiescence. Here, we demonstrate that Ino80C has a key function in the regulation of gene expression in G0 cells. We show that null mutants for two Ino80C subunits, Iec1 and Ies2, a putative subunit Arp42, a null mutant for the histone variant H2A.Z, and a null mutant for the Inositol kinase Asp1 have very similar phenotypes in quiescence. These mutants show reduced transcription genome-wide and specifically fail to activate 149 quiescence genes, of which many are localized to the subtelomeric regions. Using spike in normalized ChIP-seq experiments, we show that there is a global reduction of H2A.Z levels in quiescent wild-type cells but not in iec1∆ cells and that a subtelomeric chromosome boundary element is strongly affected by Ino80C. Based on these observations, we propose a model in which Ino80C is evicting H2A.Z from chromatin in quiescent cells, thereby inactivating the subtelomeric boundary element, leading to a reorganization of the chromosome structure and activation of genes required to survive in quiescence.
摘要：
细胞静止是单细胞和多细胞真核生物的重要生理状态。停止静止细胞进行增殖并在G0阶段停止细胞周期。使用裂变酵母作为模型生物，我们以前发现，保守的染色质重塑复合物的几个亚基，Ino80C（需要肌醇的核小体重塑因子），是静止生存所必需的。这里,我们证明Ino80C在G0细胞中的基因表达调控中具有关键功能。我们证明了两个Ino80C亚基的空突变体，Iec1和Ies2，推定的亚基Arp42，组蛋白变体H2A的无效突变体。Z,肌醇激酶Asp1的无效突变体在静止期具有非常相似的表型。这些突变体在全基因组范围内显示转录降低，并且特别不能激活149个静止基因，其中许多位于亚端粒区。在归一化ChIP-seq实验中使用尖峰，我们显示H2A的全球减少。静态野生型细胞中的Z水平，而iec1Δ细胞中则没有，并且亚端粒染色体边界元件受到Ino80C的强烈影响。基于这些观察,我们提出了一个Ino80C驱逐H2A的模型。来自静止细胞染色质的Z，从而使亚端粒边界元素失活，导致染色体结构的重组和在静止状态下生存所需的基因的激活。
