Acetylation-dependent SAGA complex dimerization promotes nucleosome acetylation and gene transcription
Acetylation-dependent SAGA complex dimerization promotes nucleosome acetylation and gene transcription
复制标题
乙酰化依赖性 SAGA 复合物二聚化促进核小体乙酰化和基因转录
DOI：
10.1038/s41594-022-00736-4
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发表时间：
2022-03-01
影响因子：
16.8
通讯作者：
Li, Shanshan
中科院分区：
文献类型：
--
作者：
Huang, Junhua;Dai, Wenjing;Li, Shanshan
细胞对其转录本进行重新编程以适应外部条件。SAGA(SPT-Ada-Gcn5乙酰转移酶)复合体是一种高度保守的转录共激活因子，在细胞生长和发育中发挥重要作用，部分是通过乙酰化组蛋白。在这里，我们揭示了酿酒酵母SAGA复合体对环境变化的自动调节机制。具体地说，SAGA复合体在三个位置(赖氨酸8，14和182)乙酰化其Ada3亚基，这三个位点被Rpd3动态去乙酰化。乙酰化的Ada3赖氨酸残基被SAGA亚基Gcn5和Spt7中的溴结构域结合，协同促进SAGA同源二聚体的形成。当细胞生长在蔗糖或磷酸盐饥饿条件下时，Ada3介导的二聚化作用被增强。一旦二聚化，SAGA有效地乙酰化核小体，促进基因转录，增强细胞对应激的抵抗力。总而言之，我们的工作揭示了SAGA结构和活动的调节机制，并为细胞如何适应环境条件提供了见解。
Cells reprogram their transcriptomes to adapt to external conditions. The SAGA (Spt-Ada-Gcn5 acetyltransferase) complex is a highly conserved transcriptional coactivator that plays essential roles in cell growth and development, in part by acetylating histones. Here, we uncover an autoregulatory mechanism of theSaccharomycescerevisiaeSAGA complex in response to environmental changes. Specifically, the SAGA complex acetylates its Ada3 subunit at three sites (lysines 8, 14 and 182) that are dynamically deacetylated by Rpd3. The acetylated Ada3 lysine residues are bound by bromodomains within SAGA subunits Gcn5 and Spt7 that synergistically facilitate formation of SAGA homo-dimers. Ada3-mediated dimerization is enhanced when cells are grown under sucrose or under phosphate-starvation conditions. Once dimerized, SAGA efficiently acetylates nucleosomes, promotes gene transcription and enhances cell resistance to stress. Collectively, our work reveals a mechanism for regulation of SAGA structure and activity and provides insights into how cells adapt to environmental conditions.