一个Drosophila Polycomb组抑制剂复合体的基甲基转移酶活性
Jürg Müller1, Craig M Hart, Nicole J Francis
1EMBL, Gene Expression Programme, Meyerhofstr. 1, 69117 Heidelberg, Germany. mueller@embl-heidelberg.de
Cell
|November 1, 2002
概括
多组 (PcG) 蛋白调节基因表达. 这项研究确定了Zeste [E(Z]蛋白的增强剂作为一个基因组甲基转移酶,在发育过程中对PcG介导的转录抑制至关重要.
科学领域:
- 发展生物学 发展生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 多组 (PcG) 蛋白质对于在发育过程中维持转录抑制至关重要.
- PcG蛋白建立抑制性染色体状态,但关键复合物的确切组成和生物化学功能尚不清楚.
- 额外的性 (ESC) 和增强性质 (E(Z) 蛋白质是关键PCG复合物的核心组成部分.
研究的目的:
- 阐明ESC-E(Z) 多组复合体的组成和生化活性.
- 为了确定E(Z) 蛋白是否具有酶活性,特别是基因组甲基转移酶功能.
- 为了研究基因组甲基化在PcG介导的基因沉默中的作用.
主要方法:
- 从Drosophila胚胎中净化ESC-E(Z) 复合体.
- 复合复合物的复合利用纯化的子单元.
- 在体外甲基转移酶试验中使用复合的复合物.
- 分析突变E(Z) 蛋白的活性和体内基因抑制.
主要成果:
- 纯化的ESC-E(Z) 复合体包括四个子单元:ESC,E(Z),NURF-55和SU(Z) 12.
- 复合的复合物表现出甲基转移酶的活性,特别是甲基化素-27的基因素H3.
- 在E(Z) SET域中的突变在体外消除了甲基转移酶活性.
- 干扰E(Z) SET域功能导致体内HOX基因抑制受损.
结论:
- 增强Zeste[E(Z]蛋白被确定为具有酶性甲基转移酶活性的Polycomb组蛋白.
- 希斯H3氨酸-27甲基化被认为是Polycomb介导的转录沉默的一个关键机制.
- 这项研究提供了生物化学证据,将PCG复合物的组成与发育的表观遗传调节联系起来.
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