一种组蛋白去乙酰化抑制剂和突变体促进人类病原体白色念珠菌的菌落类型转换。
A histone deacetylation inhibitor and mutant promote colony-type switching of the human pathogen Candida albicans.
作者信息
Klar A J, Srikantha T, Soll D R
机构信息
Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute at Frederick, DHHS, NCI, DBS, Frederick, MD 21702-1201, USA.
出版信息
Genetics. 2001 Jun;158(2):919-24. doi: 10.1093/genetics/158.2.919.
Abstract
Most strains of Candida albicans undergo high frequency phenotypic switching. Strain WO-1 undergoes the white-opaque transition, which involves changes in colony and cellular morphology, gene expression, and virulence. We have hypothesized that the switch event involves heritable changes in chromatin structure. To test this hypothesis, we transiently exposed cells to the histone deacetylase inhibitor trichostatin-A (TSA). Treatment promoted a dramatic increase in the frequency of switching from white to opaque, but not opaque to white. Targeted deletion of HDA1, which encodes a deacetylase sensitive to TSA, had the same selective effect. These results support the model that the acetylation of histones plays a selective role in regulating the switching process.
摘要
大多数白色念珠菌菌株会经历高频表型转换。WO-1菌株会发生白色-不透明转变，这涉及菌落和细胞形态、基因表达以及毒力的变化。我们推测转换事件涉及染色质结构的可遗传变化。为了验证这一假设，我们将细胞短暂暴露于组蛋白脱乙酰酶抑制剂曲古抑菌素A（TSA）。处理后，从白色转变为不透明的转换频率显著增加，但从不透明转变为白色的频率未增加。对编码对TSA敏感的脱乙酰酶的HDA1进行靶向缺失，也产生了相同的选择性作用。这些结果支持了组蛋白乙酰化在调节转换过程中起选择性作用的模型。
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