The histone deacetylase genes HDA1 and RPD3 play distinct roles in regulation of high-frequency phenotypic switching in Candida albicans
The histone deacetylase genes HDA1 and RPD3 play distinct roles in regulation of high-frequency phenotypic switching in Candida albicans
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DOI：
10.1128/jb.183.15.4614-4625.2001
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发表时间：
2001-08-01
影响因子：
3.2
通讯作者：
Soll, DR
中科院分区：
文献类型：
--
作者：
Srikantha, T;Tsai, L;Soll, DR
从白色念珠菌中克隆了5个组蛋白脱乙酰酶基因(HDA1、RPD3、HOS1、HOS2和HOS3)，并对其进行了鉴定。序列分析和与另外17个脱乙酰酶的比较，得到了由三个主要类群组成的系统发育树。在菌株WO-1中，脱乙酰酶HDA1和RPD3在白色-不透明转变的不透明阶段转录下调，HOS3在白色阶段选择性转录为2.5kb的转录产物，在不透明阶段选择性转录为2.3kb的转录产物，Hd：II和RPD3在菌株WO-1中被独立缺失，并分析了白色和不透明相之间的切换和阶段特异基因的下游调控。HDA1的缺失导致从白相到不透明相的转换频率增加，但对从不透明相到白相的转换频率没有影响。RPD3的缺失导致双向转换的频率增加。HDAI的缺失导致EFG13.2-kb转录本的白相特异性表达降低，但对WH11的白相特异性表达或OP4、SAP1和SAP3的不透明相特异性表达没有显著影响。RPD3的缺失导致OP4 SAP1和SAP3的不透明时相特异性表达减少，WH11和3.2-kb EFG1的白色时相特异性表达略有减少。HDAI和RPD3的缺失都不影响MADS盒蛋白基因MCM1的高水平白相表达和低水平不透明相表达，MCM1参与了不透明相特异基因表达的调节。此外，对其他脱乙酰基酶基因的阶段调控表达水平没有影响。这些结果表明，两个脱乙酰酶基因HDA1和RPD3在抑制开关中发挥着不同的作用，这两个基因在调控特定阶段的基因方面发挥着不同的选择性作用，而脱乙酰酶又受到开关的调节。
Five histone deacetylase genes (HDA1, RPD3, HOS1, HOS2, and HOS3) have been cloned from Candida albicans and characterized. Sequence analysis and comparison with 17 additional deacetylases resulted in a phylogenetic tree composed of three major groups. Transcription of the deacetylases HDA1 and RPD3 is downregulated in the opaque phase of the white-opaque transition in strain WO-1, HOS3 is selectively transcribed as a 2.5-kb transcript in the white phase and as a less-abundant 2.3-kb transcript in the opaque phase, HD:II and RPD3 were independently deleted in strain WO-1, and both switching between the white and opaque phases and the downstream regulation of phase-specific genes were analyzed. Deletion of HDA1 resulted in an increase in the frequency of switching from the white phase to the opaque phase, but had no effect on the frequency of switching from the opaque phase to the white phase. Deletion of RPD3 resulted in an increase in the frequency of switching in both directions. Deletion of HDAI resulted in reduced white-phase-specific expression of the EFG1 3.2-kb transcript, but had no significant effect on white-phase-specific expression of WH11 or opaque-phase-specific expression of OP4, SAP1, and SAP3. Deletion of RPD3 resulted in reduced opaque-phase-specific expression of OP4 SAP1, and SAP3 and a slight reduction of white-phase-specific expression of WH11 and 3.2-kb EFG1. Deletion of neither HDAI nor RPD3 affected the high level of white-phase expression and the low level of opaque-phase expression of the MADS box protein gene MCM1, which has been implicated in the regulation of opaque-phase-specific gene expression. In addition, there was no effect on the phase-regulated levels of expression of the other deacetylase genes. These results demonstrate that the two, deacetylase genes HDA1 and RPD3 play distinct roles in the suppression of switching, that the two play distinct and selective roles in the regulation of phase-specific genes, and that the deacetylases are in turn regulated by switching.