| 论文标题： |
Acetylation-dependent SAGA complex dimerization promotes nucleosome acetylation and gene transcription |
| 作者： |
Huang, Junhua; Dai, Wenjing; Xiao, Duncheng; Xiong, Qian; Liu, Cuifang; Hu, Jie; Ge, Feng; Yu, Xilan; Li, Shanshan |
| 出版刊物： |
NATURE STRUCTURAL & MOLECULAR BIOLOGY |
| 出版日期： |
MAR |
| 出版年份： |
2022 |
| 卷/期： |
|
| DOI： |
10.1038/s41594-022-00736-4 |
| 论文摘要： |
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 the Saccharomycescerevisiae SAGA 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. Biochemical and cellular assays show that the S. cerevisiae SAGA complex undergoes acetylation-dependent dimerization that enables the transcriptional coactivator to cooperatively acetylate nucleosomes, facilitate gene transcription and increase cell survival under stress conditions. |
