Efg1-mediated Recruitment of NuA4 to Promoters Is Required for Hypha-specific Swi/Snf Binding and Activation in Candida albicans
Efg1-mediated Recruitment of NuA4 to Promoters Is Required for Hypha-specific Swi/Snf Binding and Activation in Candida albicans
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DOI：
10.1091/mbc.e08-02-0173
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发表时间：
2008-10-01
影响因子：
3.3
通讯作者：
Chen, Jiangye
中科院分区：
文献类型：
--
作者：
Lu, Yang;Su, Chang;Chen, Jiangye
Efg1 对于人类致病真菌白色念珠菌的菌丝发育和毒力至关重要。 Efg1 如何调节基因表达尚不清楚。在这里，我们发现 Efg1 与酵母和菌丝细胞中的 H4 核小体乙酰转移酶 (NuA4) 组蛋白乙酰转移酶 (HAT) 复合物的成分相互作用。删除 NuA4 HAT 模块的亚基 YNG2 会导致核小体 H4 的乙酰化水平显着降低，导致菌丝发育严重缺陷，以及菌丝特异性基因的表达缺陷。使用染色质免疫沉淀法，在酵母和菌丝细胞的菌丝特异性基因的 UAS 区域发现了 Efg1 和 NuA4 复合物，并且 Efg1 是 NuA4 募集所必需的。启动子处的核小体 H4 乙酰化在初始菌丝诱导期间以 Efg1 依赖性方式达到峰值。我们还发现，Efg1 与菌丝特异性基因的启动子结合对于菌丝诱导过程中 Swi/Snf 染色质重塑复合物的招募至关重要。我们的数据表明，在菌丝诱导过程中，启动子处的核小体 H4 乙酰化以及随后的 Swi/Snf 结合和转录激活需要 Efg1 将 NuA4 复合物招募到菌丝特异性基因的启动子上。
Efg1 is essential for hyphal development and virulence in the human pathogenic fungus Candida albicans. How Efg1 regulates gene expression is unknown. Here, we show that Efg1 interacts with components of the nucleosome acetyltransferase of H4 (NuA4) histone acetyltransferase (HAT) complex in both yeast and hyphal cells. Deleting YNG2, a subunit of the NuA4 HAT module, results in a significant decrease in the acetylation level of nucleosomal H4 and a profound defect in hyphal development, as well as a defect in the expression of hypha-specific genes. Using chromatin immunoprecipitation, Efg1 and the NuA4 complex are found at the UAS regions of hypha-specific genes in both yeast and hyphal cells, and Efg1 is required for the recruitment of NuA4. Nucleosomal H4 acetylation at the promoters peaks during initial hyphal induction in an Efg1-dependent manner. We also find that Efg1 bound to the promoters of hypha-specific genes is critical for recruitment of the Swi/Snf chromatin remodeling complex during hyphal induction. Our data show that the recruitment of the NuA4 complex by Efg1 to the promoters of hypha-specific genes is required for nucleosomal H4 acetylation at the promoters during hyphal induction and for subsequent binding of Swi/Snf and transcriptional activation.