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NuA4 和 SWR1复合物的融合与分离控制白色念珠菌的细胞命运可塑性 |
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论文标题：Merge and separation of NuA4 and SWR1 complexes control cell fate plasticity in Candida albicans
期刊：
作者：Xiongjun Wang et al
发表时间： 2018/8/14
数字识别码：10.1186/ s41421-018-0043-0
原文链接：
表型可塑性在发育中十分普遍。白色念珠菌是人类的一种多态真菌病原体，它具有独特的能力，能够响应环境信号在单细胞形式（酵母）和多细胞形式（菌丝）之间实现快速、可逆的细胞命运转换。据报道，NuA4组蛋白乙酰转移酶活性和Hda1组蛋白去乙酰化酶活性是菌丝启动和维持所必需的。然而，尚不清楚Hda1和NuA4如何调节菌丝延伸。NuA4组蛋白乙酰转移酶和SWR1染色质重组复合物从酵母到人类是保守的，自后生动物起源以来，它们可能已经合并在一起形成一个更大的TIP60复合体。
近期，明升官网明升体育app院上海明升m88明升体育app研究院生物明升手机与细胞生物学研究所陈江野课题组在Cell Discovery上在线发表了一篇题为“NuA4 和 SWR1复合物的融合与分离控制白色念珠菌的细胞命运可塑性”的研究论文，在该研究中展示了白色念珠菌中NuA4和SWR1复合物的动态融合和分离过程。NuA4和SWR1在酵母状态下融合在一起，在菌丝状态分离成两种不同的复合物。研究证实Eaf1 K173的乙酰化控制了两种复合物之间的相互作用。在白色念珠菌中，Yaf9的YEATS结构域可以识别Eaf1的乙酰赖氨酸，并介导其与Yaf9-Eaf1的相互作用。Esa1和Hda1对Eaf1的可逆乙酰化和去乙酰化作用控制着NuA4和SWR1的融合与分离，并且这种调控是由Brg1募集Hda1到染色质而触发的，以响应维持菌丝伸长的营养信号。研究人员还观察到，在酵母-菌丝可逆转变的过程中，存在Esa1、Hda1、Swr1和H2A.Z的协调启动子关联。这是首次发现NuA4和SWR1复合物的融合调控决定着细胞的命运，并且这种调控可能在多态性真菌中是保守的。
图1：NuA4和SWR1复合物的融合和分离与白色念珠菌中的酵母-菌丝可逆转变相关。
Abstract：
Phenotypic plasticity is common in development. Candida albicans, a polymorphic fungal pathogen of humans, possesses the unique ability to achieve rapid and reversible cell fate between unicellular form (yeast) and multicellular form (hypha) in response to environmental cues. The NuA4 histone acetyltransferase activity and Hda1 histone deacetylase activity have been reported to be required for hyphal initiation and maintenance. However, how Hda1 and NuA4 regulate hyphal elongation is not clear. NuA4 histone acetyltransferase and SWR1 chromatin remodeling complexes are conserved from yeast to human, which may have merged together to form a larger TIP60 complex since the origin of metazoan. In this study, we show a dynamic merge and separation of NuA4 and SWR1 complexes in C. albicans. NuA4 and SWR1 merge together in yeast state and separate into two distinct complexes in hyphal state. We demonstrate that acetylation of Eaf1 K173 controls the interaction between the two complexes. The YEATS domain of Yaf9 in C. albicans can recognize an acetyl-lysine of the Eaf1 and mediate the Yaf9-Eaf1 interaction. The reversible acetylation and deacetylation of Eaf1 by Esa1 and Hda1 control the merge and separation of NuA4 and SWR1, and this regulation is triggered by Brg1 recruitment of Hda1 to chromatin in response nutritional signals that sustain hyphal elongation. We have also observed an orchestrated promoter association of Esa1, Hda1, Swr1, and H2A.Z during the reversible yeast–hyphae transitions. This is the first discovery of a regulated merge of the NuA4 and SWR1 complexes that controls cell fate determination and this regulation may be conserved in polymorphic fungi.
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