基因素H3氨酸9的甲基化产生HP1蛋白的结合部位
M Lachner1, D O'Carroll, S Rea
1Research Institute of Molecular Pathology, The Vienna Biocenter, Vienna, Austria.
Nature
|March 10, 2001
概括
哺乳动物甲基转移酶 (Suv39h HMTases) 通过甲基化素H3.3来为HP1蛋白产生结合点. 这种SUV39H-HP1系统对于基因沉默和维护异性染色质结构至关重要.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 染色体生物学 染色体生物学
背景情况:
- 基因组蛋白修饰调节了基因的可访问性和表达.
- 限制基因表达对于细胞和发育过程至关重要.
- 异种染色体的形成包括基因沉默和超核体染色体结构.
研究的目的:
- 为了研究哺乳动物甲基转移酶 (Suv39h HMTases) 在异染色素形成中的作用.
- 阐明将基因组甲基化与HP1蛋白结合联系起来的分子机制.
- 了解SUV39H-HP1系统如何为异色色子域做出贡献.
主要方法:
- 在体外结合试验中,使用甲基化素H3和HP1蛋白进行了结合试验.
- 在Suv39h双零小鼠纤维细胞中分析HP1蛋白与异色染色素的关联.
- 在重新引入具有催化活性的SWUV39H1 HMTase时恢复HP1关联.
主要成果:
- Suv39h HMTases在氨酸9上甲基化希斯H3,产生HP1蛋白的结合部位.
- HP1蛋白质的染色域特别识别了素H3.3上甲基化素9表位.
- HP1蛋白与异染色素的关联取决于Suv39h HMTase活性的体内活性.
- 重新引入SWUV39H1恢复HP1异染色素协会在Suv39h缺乏细胞.
结论:
- SUV39H-HP1甲基化系统为HP1与甲基化素H3.3结合提供了一个分子机制.
- 这一系统对于异色色子域在原生色素中传播至关重要.
- 由Suv39h HMTases进行的Histon H3 lysine 9甲基化是异色染色体建立和维护的关键事件.
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