Pleiotropic effects of the histone deacetylase Hos2 linked to H4-K16 deacetylation, H3-K56 acetylation, and H2A-S129 phosphorylation in Beauveria bassiana
Pleiotropic effects of the histone deacetylase Hos2 linked to H4-K16 deacetylation, H3-K56 acetylation, and H2A-S129 phosphorylation in Beauveria bassiana
复制标题
白僵菌中组蛋白脱乙酰酶 Hos2 与 H4-K16 脱乙酰化、H3-K56 乙酰化和 H2A-S129 磷酸化相关的多效性
DOI：
10.1111/cmi.12839
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发表时间：
2018-07-01
影响因子：
3.4
通讯作者：
Feng, Ming-Guang
中科院分区：
文献类型：
--
作者：
Cai, Qing;Tong, Sen-Miao;Feng, Ming-Guang
组蛋白乙酰转移酶和去乙酰化酶维持着组蛋白和非组蛋白底物上赖氨酸乙酰化/去乙酰化的动态，参与基因调控和细胞事件。Hos2 是第一类组蛋白去乙酰化酶，在酵母中对独特的组蛋白 H4-K16 位点进行去乙酰化。在这里，我们报告了在丝状真菌昆虫病原体 Beauveria bassiana 中，同源的 Hos2 除对 H4-K16 进行去乙酰化外，还参与了组蛋白 H3-K56 的乙酰化、组蛋白 H2A-S129 和细胞周期蛋白依赖性激酶 1 CDK1-Y15 的磷酸化。在缺乏 hos2 的情况下，这些位点特异性修饰表现为高乙酰化的 H4-K16、低乙酰化的 H3-K56，以及低磷酸化的 H2A-S129 和 CDK1-Y15。因此，hos2突变体对DNA损伤和氧化应激的敏感性增加，细胞周期紊乱，细胞分裂受阻，细胞大小或长度增加，分生能力降低，分生孢子特性改变，毒力减弱。这些表型变化与 DNA 损伤修复、G(1)/S 转换和 DNA 合成、菌丝分生和无性发育所必需的许多基因的显著抑制密切相关。发现的 Hos2 直接去乙酰化 H4-K16、间接修饰 H3-K56、H2A-S129 和 CDK1-Y15 的能力，使人们对 Hos2 在昆虫真菌病原体基因组稳定性和各种细胞事件中的微妙调控作用有了新的认识。
Histone acetyltransferases and deacetylases maintain dynamics of lysine acetylation/deacetylation on histones and nonhistone substrates involved in gene regulation and cellular events. Hos2 is a Class I histone deacetylases that deacetylates unique histone H4-K16 site in yeasts. Here, we report that orthologous Hos2 deacetylates H4-K16 and is also involved in the acetylation of histone H3-K56 and the phosphorylation of histone H2A-S129 and cyclin-dependent kinase 1 CDK1-Y15 in Beauveria bassiana, a filamentous fungal insect pathogen. These site-specific modifications are evidenced with hyperacetylated H4-K16, hypoacetylated H3-K56, and both hypophosphorylated H2A-S129 and CDK1-Y15 in absence of hos2. Consequently, the hos2 mutant suffered increased sensitivities to DNA-damaging and oxidative stresses, disturbed cell cycle, impeded cytokinesis, increased cell size or length, reduced conidiation capacity, altered conidial properties, and attenuated virulence. These phenotypic changes correlated well with dramatic repression of many genes that are essential for DNA damage repair, G(1)/S transition and DNA synthesis, hyphal septation, and asexual development. The uncovered ability for Hos2 to directly deacetylate H4-K16 and to indirectly modify H3-K56, H2A-S129, and CDK1-Y15 provides novel insight into more subtle regulatory role for Hos2 in genomic stability and diverse cellular events in the fungal insect pathogen than those revealed previously in nonentomophathogenic fungi.