Plant Homeodomain Genes Play Important Roles in Cryptococcal Yeast-Hypha Transition
Plant Homeodomain Genes Play Important Roles in Cryptococcal Yeast-Hypha Transition
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DOI：
10.1128/aem.01732-17
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发表时间：
2018-05-01
影响因子：
4.4
通讯作者：
Lin, Xiaorong
中科院分区：
文献类型：
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作者：
Meng, Yunfang;Fan, Yumeng;Lin, Xiaorong
新型隐球菌是一种重要的机会致病真菌。与许多二型真菌病原体一样，C.新形菌可以经历从酵母形式到菌丝形式的形态转变，并且其形态型与其毒力紧密相关。虽然一些控制形态发生的遗传因素已被确定，但对这一过程中的表观遗传调控知之甚少。具有植物同源结构域（PHD）指的蛋白质是真核生物中结构保守的结构域，其首先在植物中被鉴定并且已知参与阅读并影响染色质修饰。在这里，我们研究了PHD指家族基因在隐球菌交配和酵母菌丝转换中的作用。在隐球菌基因组中发现16个PHD指状结构域分布在15个基因中，其中ZNF 1 α和RUM 1 α两个基因位于交配型位点。我们删除了这15个PHD基因，并研究了它们的破坏对隐球菌形态发生的影响。五个PHD指基因的缺失显著影响了表达。rum 1 α Delta和znf 1 α Delta突变体显示出增强的启动表达的能力，但削弱了维持丝状生长的能力。bye 1 Delta和phd 11 Delta突变体表现出增强的趋化，而set 302 Delta突变体表现出降低的趋化。这五个基因在相应的无效突变体中的异位过表达部分或完全恢复了表达缺陷。此外，我们证明了Phd 11，抑制剂的抑制，调节酵母菌丝过渡通过已知的主调节Znf 2。这些结果表明表观遗传调控在控制C.重要性已知形态型对隐球菌与各种宿主（包括哺乳动物宿主）的相互作用具有深远影响。新型隐球菌的酵母形式被认为是毒性形式，而其菌丝形式在隐球菌病的哺乳动物模型中被减弱。虽然已经确定了一些隐球菌形态发生的关键基因调控因子，但对这一过程中的表观遗传调控知之甚少。鉴于植物同源结构域（PHD）指蛋白参与阅读和影响染色质修饰，并且它们的功能在C.在隐球菌属新生隐球菌中，我们研究了15个PHD指状基因在隐球菌交配和酵母-菌丝转化中的作用。其中五个深刻地影响到履行作为一个抑制剂或激活剂。Phd 11是一种抑制子，通过Znf 2调节这一过程，Znf 2是一种已知的形态发生主调节因子。因此，表观遗传调控，加上遗传调控，控制这个酵母菌丝过渡事件。
Cryptococcus neoformans is a major opportunistic fungal pathogen. Like many dimorphic fungal pathogens, C. neoformans can undergo morphological transition from the yeast form to the hypha form, and its morphotype is tightly linked to its virulence. Although some genetic factors controlling morphogenesis have been identified, little is known about the epigenetic regulation in this process. Proteins with the plant homeodomain (PHD) finger, a structurally conserved domain in eukaryotes, were first identified in plants and are known to be involved in reading and effecting chromatin modification. Here, we investigated the role of the PHD finger family genes in Cryptococcus mating and yeast-hypha transition. We found 16 PHD finger domains distributed among 15 genes in the Cryptococcus genome, with two genes, ZNF1 alpha and RUM1 alpha, located in the mating type locus. We deleted these 15 PHD genes and examined the impact of their disruption on cryptococcal morphogenesis. The deletion of five PHD finger genes dramatically affected filamentation. The rum1 alpha Delta and znf1 alpha Delta mutants showed enhanced ability to initiate filamentation but impaired ability to maintain filamentous growth. The bye1 Delta and the phd11 Delta mutants exhibited enhanced filamentation, while the set302 Delta mutants displayed reduced filamentation. Ectopic overexpression of these five genes in the corresponding null mutants partially or completely restored the defect in filamentation. Furthermore, we demonstrated that Phd11, a suppressor of filamentation, regulates the yeast-hypha transition through the known master regulator Znf2. The findings indicate the importance of epigenetic regulation in controlling dimorphic transition in C. neoformans.IMPORTANCE Morphotype is known to have a profound impact on cryptococcal interaction with various hosts, including mammalian hosts. The yeast form of Cryptococcus neoformans is considered the virulent form, while its hyphal form is attenuated in mammalian models of cryptococcosis. Although some genetic regulators critical for cryptococcal morphogenesis have been identified, little is known about epigenetic regulation in this process. Given that plant homeodomain (PHD) finger proteins are involved in reading and effecting chromatin modification and their functions are unexplored in C. neoformans, we investigated the roles of the 15 PHD finger genes in Cryptococcus mating and yeast-hypha transition. Five of them profoundly affect filamentation as either a suppressor or an activator. Phd11, a suppressor of filamentation, regulates this process via Znf2, a known master regulator of morphogenesis. Thus, epigenetic regulation, coupled with genetic regulation, controls this yeast-hypha transition event.