Department of Biological Chemistry, University of California, Irvine, CA 92697, USA.
Mol Microbiol. 2011 Aug;81(4):1078-91. doi: 10.1111/j.1365-2958.2011.07754.x. Epub 2011 Jul 12.
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 downregulated 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.
不同基因型的细胞如何形成以及遗传率如何维持是生物学中的一个基本问题。我们利用白色-不透明转换在白色念珠菌中作为研究细胞类型形成和维持机制的系统。每种细胞类型都有可追踪的特征，这些特征可以在许多细胞分裂中保持。细胞类型的特化受连锁转录反馈回路的控制，其中 Wor1 是不透明细胞类型的主调控因子。在这里，我们表明，编码组蛋白 H3K56 的乙酰转移酶 RTT109 的缺失会损害随机和环境刺激的白色-不透明转换。WOR1 的异位表达在很大程度上绕过了对 RTT109 的需求，但缺乏 RTT109 的不透明细胞无法维持。我们还发现烟酰胺诱导不透明细胞形成，而烟酰胺的这种活性需要 RTT109。降低编码 H3K56 去乙酰化酶的 HST3 的拷贝数也会导致不透明形成增加。我们进一步表明，在存在遗传毒素的情况下，Hst3 水平下调，并且异位表达 HST3 会阻止遗传毒素诱导的转换。这一发现将遗传毒素诱导的转换与 Hst3 调节联系起来。总之，这些发现表明 RTT109 和 HST3 基因在白色念珠菌中白色-不透明转换的调节中发挥着重要作用。
