Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
Mol Biol Cell. 2012 Jul;23(14):2805-17. doi: 10.1091/mbc.E12-04-0278. Epub 2012 May 23.
In Saccharomyces cerevisiae, the transcriptional program triggered by cell wall stress is coordinated by Slt2/Mpk1, the mitogen-activated protein kinase (MAPK) of the cell wall integrity (CWI) pathway, and is mostly mediated by the transcription factor Rlm1. Here we show that the SWI/SNF chromatin-remodeling complex plays a critical role in orchestrating the transcriptional response regulated by Rlm1. swi/snf mutants show drastically reduced expression of cell wall stress-responsive genes and hypersensitivity to cell wall-interfering compounds. On stress, binding of RNA Pol II to the promoters of these genes depends on Rlm1, Slt2, and SWI/SNF. Rlm1 physically interacts with SWI/SNF to direct its association to target promoters. Finally, we observe nucleosome displacement at the CWI-responsive gene MLP1/KDX1, which relies on the SWI/SNF complex. Taken together, our results identify the SWI/SNF complex as a key element of the CWI MAPK pathway that mediates the chromatin remodeling necessary for adequate transcriptional response to cell wall stress.
在酿酒酵母中,由细胞壁应激触发的转录程序由 Slt2/Mpk1 协调,Slt2/Mpk1 是细胞壁完整性 (CWI) 途径的丝裂原激活蛋白激酶 (MAPK),主要由转录因子 Rlm1 介导。在这里,我们表明 SWI/SNF 染色质重塑复合物在协调由 Rlm1 调节的转录反应中起着关键作用。swi/snf 突变体表现出细胞壁应激反应基因的表达明显降低,并且对细胞壁干扰化合物敏感。在应激条件下,RNA Pol II 与这些基因启动子的结合依赖于 Rlm1、Slt2 和 SWI/SNF。Rlm1 与 SWI/SNF 相互作用,以指导其与靶启动子结合。最后,我们观察到依赖于 SWI/SNF 复合物的 CWI 反应基因 MLP1/KDX1 的核小体位移。总之,我们的结果确定了 SWI/SNF 复合物作为 CWI MAPK 途径的关键组成部分,该途径介导了染色质重塑,这对于细胞壁应激的适当转录反应是必要的。