Fillingham Jeffrey, Kainth Pinay, Lambert Jean-Philippe, van Bakel Harm, Tsui Kyle, Peña-Castillo Lourdes, Nislow Corey, Figeys Daniel, Hughes Timothy R, Greenblatt Jack, Andrews Brenda J
Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Canada.
Mol Cell. 2009 Aug 14;35(3):340-51. doi: 10.1016/j.molcel.2009.06.023.
We describe a fluorescent reporter system that exploits the functional genomic tools available in budding yeast to systematically assess consequences of genetic perturbations on gene expression. We used our Reporter-Synthetic Genetic Array (R-SGA) method to screen for regulators of core histone gene expression. We discovered that the histone chaperone Rtt106 functions in a pathway with two other chaperones, Asf1 and the HIR complex, to create a repressive chromatin structure at core histone promoters. We found that activation of histone (HTA1) gene expression involves both relief of Rtt106-mediated repression by the activity of the histone acetyltransferase Rtt109 and restriction of Rtt106 to the promoter region by the bromodomain-containing protein Yta7. We propose that the maintenance of Asf1/HIR/Rtt106-mediated repressive chromatin domains is the primary mechanism of cell-cycle regulation of histone promoters. Our data suggest that this pathway may represent a chromatin regulatory mechanism that is broadly used across the genome.
我们描述了一种荧光报告系统，该系统利用芽殖酵母中可用的功能基因组工具来系统地评估基因扰动对基因表达的影响。我们使用报告基因 - 合成遗传阵列（R - SGA）方法筛选核心组蛋白基因表达的调节因子。我们发现组蛋白伴侣Rtt106与另外两个伴侣Asf1和HIR复合物在一条途径中发挥作用，在核心组蛋白启动子处形成抑制性染色质结构。我们发现组蛋白（HTA1）基因表达的激活既涉及组蛋白乙酰转移酶Rtt109的活性对Rtt106介导的抑制的解除，也涉及含溴结构域蛋白Yta7将Rtt106限制在启动子区域。我们提出，Asf1/HIR/Rtt106介导的抑制性染色质结构域的维持是组蛋白启动子细胞周期调控的主要机制。我们的数据表明，该途径可能代表一种在全基因组中广泛使用的染色质调节机制。
