Regulation of white and opaque cell-type formation in Candida albicans by Rtt109 and Hst3.
Regulation of white and opaque cell-type formation in Candida albicans by Rtt109 and Hst3.
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DOI：
10.1111/j.1365-2958.2011.07754.x
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发表时间：
2011-08
影响因子：
3.6
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Stevenson JS;Liu H
相同基因型的不同细胞类型是如何形成和保持遗传性的是生物学中的一个基本问题。我们利用白色念珠菌中的白色不透明转换作为一个系统来研究细胞类型形成和维持的机制。每一种细胞类型都具有易处理的特征，这些特征在多次细胞分裂中得以保持。细胞类型特化是在互锁的转录反馈环的控制下，其中Wor1是不透明细胞类型的主调节器。在这里，我们表明，RTT109，编码组蛋白H3K56的乙酰转移酶的缺失，损害随机和环境刺激的白色不透明开关。W0R1的异位表达大多绕过对RTT109的需要，但缺乏RTT109的不透明细胞不能维持。我们还发现烟酰胺诱导不透明细胞形成，烟酰胺的这种活性需要RTT109。减少编码H3K56脱乙酰酶的HST 3的拷贝数也导致增加的不透明形成。我们进一步表明，HST 3水平下调的存在下，遗传毒素和异位表达的HST 3块遗传毒素诱导的开关。这一发现将遗传毒素诱导的转换与Hst 3调节联系起来。这些发现表明RTT109和HST3基因在调节C.白色念珠菌
How different cell types with the same genotype are formed and heritability maintained is a fundamental question in biology. We utilized white-opaque switching in Candida albicans as a system to study mechanisms of cell type formation and maintenance. Each cell type has tractable characters, which are maintained over many cell divisions. Cell type specification is under the control of interlocking transcriptional feedback loops, with Wor1 being the master regulator of the opaque cell type. Here we show that deletion of RTT109, encoding the acetyltransferase for histone H3K56, impairs stochastic and environmentally stimulated white-opaque switching. Ectopic expression of WOR1 mostly bypasses the requirement for RTT109, but opaque cells lacking RTT109 cannot be maintained. We have also discovered that nicotinamide induces opaque cell formation, and this activity of nicotinamide requires RTT109. Reducing the copy number of HST3, which encodes the H3K56 deacetylase, also leads to increased opaque formation. We further show that the Hst3 level is down regulated in the presence of genotoxins and ectopic expression of HST3 blocks genotoxin induced switching. This finding links genotoxin induced switching to Hst3 regulation. Together these findings suggest RTT109 and HST3 genes play an important role in the regulation of white-opaque switching in C. albicans.