Distinct and Redundant Roles of the Two MYST Histone Acetyltransferases Esa1 and Sas2 in Cell Growth and Morphogenesis of Candida albicans
Distinct and Redundant Roles of the Two MYST Histone Acetyltransferases Esa1 and Sas2 in Cell Growth and Morphogenesis of Candida albicans
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两种 MYST 组蛋白乙酰转移酶 Esa1 和 Sas2 在白色念珠菌细胞生长和形态发生中的独特和冗余作用
DOI：
10.1128/ec.00275-12
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发表时间：
2013-03-01
期刊：
影响因子：
--
通讯作者：
Chen, Jiangye
中科院分区：
文献类型：
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作者：
Wang, Xiongjun;Chang, Peng;Chen, Jiangye
摘要白色念珠菌既是一种无害的共生生物，又是一种致病菌，与人类密切相关。对人体温度的适应对其生长和形态发生极其重要。酿酒酵母Esa1是组蛋白乙酰转移酶家族成员之一，也是NuA4复合体的催化亚单位，它及其在其他真核生物中的同源物对细胞生长是必不可少的。为了研究两个myst家族HAT ESA1和SAS2在白念珠菌中的功能，我们删除了白念珠菌基因组中的ESA1和SAS2，并进行了细胞生长分析。我们的结果表明，白念珠菌Esa1对一般生长不是必需的，但对丝状生长是必需的。ESA1/ESA1突变细胞对热、遗传毒性和氧化应激敏感，但对冷、渗透和细胞壁应激耐受。相反，SAS2/SAS2突变体适应较高温度的生长，并促进较低温度下的细丝形成，类似于高表达ESA1的白色念珠菌的表型。同时缺失ESA1和SAS2的细胞无法存活，反映了细胞生长过程中的功能冗余。白念珠菌Esa1和SAS2对H4K5、H4K12和H4K16的组蛋白乙酰化有明显的协同作用。ESA1主要促进H4K5和H4K12的乙酰化，而SAS2主要促进H4K16的乙酰化。我们的发现表明，白念珠菌Esa1和SAS2在细胞生长和形态发生中扮演相反的角色，而在组蛋白乙酰化和基因调控中起协同作用。
ABSTRACT Candida albicans is associated with humans, as both a harmless commensal organism and a pathogen. Adaption to human body temperature is extremely important for its growth and morphogenesis. Saccharomyces cerevisiae Esa1, a member of the MYST family HATs (histone acetyltransferases) and the catalytic subunit of the NuA4 complex, and its homologues in other eukaryotes have been shown to be essential for cell growth. To investigate the functional roles of two MYST family HATs, Esa1 and Sas2 in C. albicans, we deleted ESA1 and SAS2 in the C. albicans genome and performed cell growth analyses. Our results demonstrated that C. albicans Esa1 is not essential for general growth but is essential for filamentous growth. The esa1/esa1 mutant cells exhibited sensitivity to thermal, genotoxic, and oxidative stresses but tolerance to cold, osmotic, and cell wall stresses. In contrast, the sas2/sas2 mutant adapted to growth at higher temperatures and promoted filament formation at lower temperatures, resembling the phenotype of a C. albicans strain overexpressing ESA1. Cells with deletions of both ESA1 and SAS2 were inviable, reflecting the functional redundancy in cell growth. C. albicans Esa1 and Sas2 have distinct and synergistic effects on histone acetylation at H4K5, H4K12, and H4K16. Esa1 contributes mainly to acetylation of H4K5 and H4K12, whereas Sas2 contributes to acetylation of H4K16. Our findings suggest that C. albicans Esa1 and Sas2 play opposite roles in cell growth and morphogenesis and contribute coordinately to histone acetylation and gene regulation.