Identification of novel activation mechanisms for FLO11 regulation in Saccharomyces cerevisiae
Identification of novel activation mechanisms for FLO11 regulation in Saccharomyces cerevisiae
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DOI：
10.1534/genetics.107.081315
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发表时间：
2008-01-01
期刊：
影响因子：
3.3
通讯作者：
Ibeas, Jose I.
中科院分区：
文献类型：
--
作者：
Barrales, Ramon R.;Jimenez, Juan;Ibeas, Jose I.
粘附素在真核微生物对其宿主环境的细胞反应中起着核心作用。在病原体如念珠菌属（Candida spp.）和其它真菌中，粘附素负责粘附到哺乳动物组织，并且在酵母属中，酵母还赋予对固体表面和其它酵母细胞的粘附性。FLO11，在酿酒酵母中鉴定的主要粘附素的分析揭示了复杂的机制，涉及遗传和表观遗传调控，支配这个关键基因的表达。我们设计了一个全基因组筛选，以确定芽殖酵母中这种关键粘附素的调节因子。我们利用了一个特定的FLO11等位基因，赋予非常高的FLO11表达水平的野生型“flor”菌株的S。啤酒。我们筛选的突变体，废除增加FLO11表达的等位基因使用的特征蓬松菌落表型的损失和报告质粒含有GFP控制相同的FLO11启动子。使用这种方法，我们分离了几个基因，其功能是必不可少的，以维持FLO11的表达。除了先前表征的激活剂，我们确定了一些新的FLO11激活剂，这揭示了pH响应途径和染色质重塑复合物作为参与FLO11激活的中心要素。
Adhesins play a central role in the cellular response of eukaryotic microorganisms to their host environment. In pathogens such as Candida spp. and other fungi, adhesins are responsible for adherence to mammalian tissues, and in Saccharomyces spp. yeasts also confer adherence to solid Surfaces and to other yeast cells. The analysis of FLO11, the main adhesin identified in Saccharomyces cerevisiae, has revealed complex mechanisms, involving both genetic and epigenetic regulation, governing the expression of this critical gene. We designed a genomewide screen to identify ne v regulators of this pivotal adhesin in budding yeasts. We took advantage of a specific FLO11 allele that confers very high levels of FLO11 expression to wild "flor" strains of S. cerevisiae. We screened for mutants that abrogated the increased FLO11 expression of this allele using the loss of the characteristic fluffy-colony phenotype and a reporter plasmid containing GFP controlled by the same FLO11 promoter. Using this approach, we isolated several genes whose function was essential to maintain the expression of FLO11. In addition to previously characterized activators, we identified a number of novel FLO11 activators, which reveal the pH response pathway and chromatin-remodeling complexes as central elements involved in FLO11 activation.