在异性染色蛋白的形成过程中,SIRT1调节了组织素甲基转移酶SUV39H1的作用
Alejandro Vaquero1, Michael Scher, Hediye Erdjument-Bromage
1Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Jersey 08854, USA.
Nature
|November 16, 2007
概括
促进选择性异染色素的形成,素脱乙酶SIRT1直接向并脱乙化甲基转移酶SUV39H1.1. 这种相互作用增强了SUV39H1的活性,增加了H3K9me3的水平,并影响了异染色蛋白1的局部化.
科学领域:
- 表观遗传学和染色体生物学
- 基因调节的分子机制
背景情况:
- 选择性色胺动态调节基因转录,与构成性色胺或 euchromatin 不同.
- 赛尔图因1 (SIRT1) 和变异3-9同类抑制剂1 (SUV39H1) 是选择性异染色素形成的关键酶.
- SUV39H1催化H3K9me3,这是异色染色素的标志,而SIRT1脱乙基因组H4并影响H3K9me3水平.
研究的目的:
- 阐明SIRT1影响H3K9me3水平的分子机制.
- 调查SIRT1和SUV39H1.1.之间的直接相互作用和功能关系.
- 了解SIRT1是如何调节SUV39H1活动的,以及它在异性染色素形成中的作用.
主要方法:
- 生物化学试验证明SIRT1和SUV39H1.1.之间的直接相互作用.
- 在体外和体内实验中评估SIRT1脱乙对SUV39H1活性的影响.
- 分析H3K9me3水平和异染色蛋白1局部化在SIRT1.1的存在和缺席.
主要成果:
- 在其催化SET域内,SIRT1直接与SUV39H1在lysine 266相互作用,招募并脱乙.
- 通过SIRT1介导的SUV39H1脱乙增强了其甲基转移酶活性,导致H3K9me3.3的增加.
- 失去SIRT1功能会影响SUV39H1依赖的H3K9me3积累和异色素蛋白1定位.
结论:
- 通过脱乙烯化,SIRT1直接调节与异染色质相关的甲基转移酶SUV39H1的活性.
- 这种SIRT1和SUV39H1之间的功能联系提供了一种控制H3K9me3水平和选择性异质染色素的新机制.
- 这些发现凸显了在表观遗传基因调节中,基因素脱乙烯化和甲基化之间的关键相互作用.
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