Srikantha T, Tsai L, Daniels K, Klar A J, Soll D R
Department of Biological Sciences, University of Iowa, Iowa City, IA 52242, USA.
J Bacteriol. 2001 Aug;183(15):4614-25. doi: 10.1128/JB.183.15.4614-4625.2001.
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 down-regulated 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. HDA1 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 HDA1 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 HDA1 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.
已从白色念珠菌中克隆并鉴定了五个组蛋白脱乙酰酶基因（HDA1、RPD3、HOS1、HOS2和HOS3）。序列分析以及与另外17种脱乙酰酶的比较产生了一个由三个主要组构成的系统发育树。在菌株WO-1的白色-不透明转变的不透明阶段，脱乙酰酶HDA1和RPD3的转录被下调。HOS3在白色阶段选择性转录为2.5 kb的转录本，在不透明阶段转录为丰度较低的2.3 kb转录本。在菌株WO-1中独立缺失HDA1和RPD3，并分析了白色和不透明阶段之间的转换以及阶段特异性基因的下游调控。缺失HDA1导致从白色阶段转换到不透明阶段的频率增加，但对从不透明阶段转换到白色阶段的频率没有影响。缺失RPD3导致两个方向的转换频率增加。缺失HDA1导致EFG1 3.2 kb转录本的白色阶段特异性表达降低，但对WH11的白色阶段特异性表达或OP4、SAP1和SAP3的不透明阶段特异性表达没有显著影响。缺失RPD3导致OP4、SAP1和SAP3的不透明阶段特异性表达降低，以及WH11和3.2 kb EFG1的白色阶段特异性表达略有降低。缺失HDA1和RPD3均不影响MADS盒蛋白基因MCM1的高水平白色阶段表达和低水平不透明阶段表达，该基因与不透明阶段特异性基因表达的调控有关。此外，对其他脱乙酰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在抑制转换中发挥不同作用，在阶段特异性基因的调控中发挥不同且选择性的作用，并且脱乙酰酶又受转换调控。
