Howard Hughes Medical Institute, Harvard University Faculty of Arts and Sciences Center for Systems Biology, Cambridge, Massachusetts 02138, USA.
G3 (Bethesda). 2012 Sep;2(9):1129-36. doi: 10.1534/g3.112.003251. Epub 2012 Sep 1.
When challenged with osmotic shock, Saccharomyces cerevisiae induces hundreds of genes, despite a concurrent reduction in overall transcriptional capacity. The stress-responsive MAP kinase Hog1 activates expression of specific genes through interactions with chromatin remodeling enzymes, transcription factors, and RNA polymerase II. However, it is not clear whether Hog1 is involved more globally in modulating the cell's transcriptional program during stress, in addition to activating specific genes. Here we show that large-scale redistribution of RNA Pol II from housekeeping to stress genes requires Hog1. We demonstrate that decreased RNA Pol II occupancy is the default outcome for highly expressed genes upon stress and that Hog1 is partially required for this effect. We find that Hog1 and RNA Pol II colocalize to open reading frames that bypass global transcriptional repression. These activation targets are specified by promoter binding of two osmotic stress-responsive transcription factors. The combination of reduced global transcription with a gene-specific override mechanism allows cells to rapidly switch their transcriptional program in response to stress.
当面临渗透冲击时，酿酒酵母诱导数百个基因的表达，尽管同时整体转录能力降低。应激响应的 MAP 激酶 Hog1 通过与染色质重塑酶、转录因子和 RNA 聚合酶 II 的相互作用激活特定基因的表达。然而，目前尚不清楚 Hog1 是否除了激活特定基因外，还更广泛地参与调节细胞在应激过程中的转录程序。在这里，我们表明，RNA 聚合酶 II 从管家基因到应激基因的大规模重新分配需要 Hog1。我们证明，在应激下，高表达基因的 RNA 聚合酶 II 占有率降低是默认结果，而 Hog1 对此有部分作用。我们发现，Hog1 和 RNA 聚合酶 II 共定位到开放阅读框，绕过全局转录抑制。这些激活靶标由两个渗透应激响应转录因子的启动子结合指定。减少全局转录与基因特异性覆盖机制的结合允许细胞快速响应应激而切换其转录程序。
