Sanz Ana Belén, García Raúl, Rodríguez-Peña José Manuel, Nombela César, Arroyo Javier
Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, IRYCIS, 28040 Madrid, Spain.
Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, IRYCIS, 28040 Madrid, Spain
Nucleic Acids Res. 2016 Sep 6;44(15):7159-72. doi: 10.1093/nar/gkw324. Epub 2016 Apr 25.
The transcriptional response of Saccharomyces cerevisiae to cell wall stress is mainly mediated by the cell wall integrity (CWI) pathway through the MAPK Slt2 and the transcription factor Rlm1. Once activated, Rlm1 interacts with the chromatin remodeling SWI/SNF complex which locally alters nucleosome positioning at the target promoters. Here we show that the SAGA complex plays along with the SWI/SNF complex an important role for eliciting both early induction and sustained gene expression upon stress. Gcn5 co-regulates together with Swi3 the majority of the CWI transcriptional program, except for a group of genes which are only dependent on the SWI/SNF complex. SAGA subunits are recruited to the promoter of CWI-responsive genes in a Slt2, Rlm1 and SWI/SNF-dependent manner. However, Gcn5 mediates acetylation and nucleosome eviction only at the promoters of the SAGA-dependent genes. This process is not essential for pre-initiation transcriptional complex assembly but rather increase the extent of the remodeling mediated by SWI/SNF. As a consequence, H3 eviction and Rlm1 recruitment is completely blocked in a swi3Δ gcn5Δ double mutant. Therefore, SAGA complex, through its histone acetylase activity, cooperates with the SWI/SNF complex for the mandatory nucleosome displacement required for full gene expression through the CWI pathway.
酿酒酵母对细胞壁应激的转录反应主要由细胞壁完整性(CWI)途径通过丝裂原活化蛋白激酶Slt2和转录因子Rlm1介导。一旦被激活,Rlm1就会与染色质重塑SWI/SNF复合物相互作用,该复合物会局部改变靶启动子处的核小体定位。在这里,我们表明SAGA复合物与SWI/SNF复合物一起在应激时引发早期诱导和持续基因表达方面发挥重要作用。Gcn5与Swi3共同调节大多数CWI转录程序,但有一组基因仅依赖于SWI/SNF复合物。SAGA亚基以Slt2、Rlm1和SWI/SNF依赖的方式被招募到CWI反应基因的启动子上。然而,Gcn5仅在SAGA依赖基因的启动子处介导乙酰化和核小体驱逐。这个过程对于转录起始前复合物的组装不是必需的,而是增加了由SWI/SNF介导的重塑程度。因此,在swi3Δ gcn5Δ双突变体中,H3驱逐和Rlm1招募被完全阻断。因此,SAGA复合物通过其组蛋白乙酰转移酶活性,与SWI/SNF复合物协同作用,实现通过CWI途径进行全基因表达所需的强制性核小体位移。