Bistable expression of WOR1, a master regulator of white-opaque switching in Candida albicans
Bistable expression of WOR1, a master regulator of white-opaque switching in Candida albicans
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DOI：
10.1073/pnas.0605270103
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发表时间：
2006-08-22
影响因子：
11.1
通讯作者：
Liu, Haoping
中科院分区：
文献类型：
--
作者：
Huang, Guanghua;Wang, Huafeng;Liu, Haoping
白色念珠菌（Candida albicans）是一种常见的微生物，是人类的病原菌，它可以在白色相和不透明相之间随机转换，不存在中间相。白色和不透明相具有不同的细胞形状和基因表达程序。一旦转换，每个阶段对于许多细胞分裂都是稳定的。白色不透明转换是在α 1-α 2抑制下进行的，因此只发生在a或a细胞中。控制转换的机制尚不清楚。在这里，我们将Wor 1（白色不透明调节器1）确定为白色不透明切换的主调节器。W 0 R1的缺失阻断了不透明细胞的形成。W 0 R1的异位表达将a或a细胞中的所有细胞转化为稳定的不透明细胞。此外，WOR 1在α/α细胞中的异位表达足以诱导不透明细胞形成。重要的是，W 0 R1表达显示全或无模式。在白色细胞中检测不到，在不透明细胞中高度表达。Wor 1的异位表达诱导了W 0 R1基因座的W 0 R1的转录，这与不透明相的转换相关。我们提出了反馈调节WOR 1转录的遗传证据。反馈调节解释了白色不透明切换的随机性和随机性。
Candida albicans, a commensal organism and a pathogen of humans, can switch stochastically between a white phase and an opaque phase without an intermediate phase. The white and opaque phases have distinct cell shapes and gene expression programs. Once switched, each phase is stable for many cell divisions. White-opaque switching is under a1-alpha 2 repression and therefore only happens in a or a cells. Mechanisms that control the switching are unknown. Here, we identify Wor1 (white-opaque regulator 1) as a master regulator of white-opaque switching. The deletion of WOR1 blocks opaque cell formation. The ectopic expression of WOR1 converts all cells to stable opaque cells in a or a cells. In addition, the ectopic expression of WOR1 in a/alpha cells is sufficient to induce opaque cell formation. Importantly, WOR1 expression displays an all-or-none pattern. It is undetectable in white cells, and it is highly expressed in opaque cells. The ectopic expression of Wor1 induces the transcription of WOR1 from the WOR1 locus, which correlates with the switch to opaque phase. We present genetic evidence for feedback regulation of WOR1 transcription. The feedback regulation explains the bistable and stochastic nature of white-opaque switching.