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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Epigenetic properties of white-opaque switching in Candida albicans are based on a self-sustaining transcriptional feedback loop
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Epigenetic properties of white-opaque switching in Candida albicans are based on a self-sustaining transcriptional feedback loop

机译：白色念珠菌中白不透明转换的表观遗传特性基于自我维持的转录反馈环

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摘要

White-opaque switching in the human fungal pathogen Candida albicans is an alternation between two distinct types of cells, white and opaque. White and opaque cells differ in their appearance under the microscope, the genes they express, their mating behaviors, and the host tissues for which they are best suited. Each state is heritable for many generations, and switching between states occurs stochastically, at low frequency. In this article, we identify a master regulator of white-opaque switching (Wor1), and we show that this protein is a transcriptional regulator that is needed to both establish and maintain the opaque state. We show that in opaque cells, Wor1 forms a positive feedback loop: it binds its own DNA regulatory region and activates its own transcription leading to the accumulation of high levels of Wor1. We further show that this feedback loop is self-sustaining: Once activated, it persists for many generations. We propose that this Wor1 feedback loop accounts, at least in part, for the heritability of the opaque state. In contrast, white cells (and their descendents) lack appreciable levels of Wor1, and the feedback loop remains inactive. Thus, this simple model can account for both the heritability of the white and opaque states and the stochastic nature of the switching between them.
机译：人类真菌病原体白色念珠菌中的白色不透明转换是两种不同类型的细胞（白色和不透明）之间的交替。白细胞和不透明细胞在显微镜下的外观，它们表达的基因，它们的交配行为以及最适合它们的宿主组织不同。每个状态都可以遗传很多代，并且状态之间的切换是随机发生的，频率较低。在本文中，我们确定了白不透明开关（Wor1）的主要调节子，并且我们证明了该蛋白是一种转录调节子，既可以建立也可以保持不透明状态。我们显示，在不透明的细胞中，Wor1形成一个正反馈环：它结合自己的DNA调节区并激活其自身的转录，从而导致高水平Wor1的积累。我们进一步表明，这种反馈循环是自我维持的：一旦激活，它就会持续存在很多代。我们建议此Wor1反馈循环至少部分地说明了不透明状态的遗传性。相比之下，白细胞（及其后代）缺乏明显的Wor1水平，并且反馈回路保持不活动状态。因此，这个简单的模型可以说明白色和不透明状态的可遗传性以及它们之间切换的随机性。

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