在C. elegans中,H3K4三甲基化复合物的成员以依赖生殖系的方式调节了C. elegans的寿命
Eric L Greer1, Travis J Maures, Anna G Hauswirth
1Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.
Nature
|June 18, 2010
概括
衰老的表观遗传调节涉及组织蛋白甲基化. 在C. elegans中,ASH-2复合体,它在lysine 4 (H3K4) 修改了组素H3,调节了寿命,缺陷通过生殖系延长了寿命.
科学领域:
- 表观遗传学和分子生物学
- 老年学和衰老研究研究.
- 发育生物学是发展生物学.
背景情况:
- 衰老受到表观遗传修饰的影响,特别是基因组变化.
- 虽然已知胰岛素脱甲基化在衰老中的作用,但其他修改,如胰岛素甲基化,理解程度较低.
- 基因组甲基化对发育和干细胞多能性至关重要,调节者与模型生物的衰老有关.
研究的目的:
- 为了确定Caenorhabditis elegans中寿命的表观遗传调节者.
- 为了研究素甲基化,特别是H3K4三甲基化在衰老中的作用.
- 阐明基因组甲基化复合物影响寿命的机制.
主要方法:
- 在肥沃的Caenorhabditis elegans.中进行定向RNA干扰 (RNAi) 选.
- 基因操纵ASH-2三体复合物的组成部分 (ASH-2,WDR-5,SET-2) 和H3K4脱甲基酶 (RBR-2).
- 对寿命延长的分析以及对生殖线完整性和卵子生产的依赖.
主要成果:
- 在ASH-2复合体成员 (ASH-2,WDR-5,SET-2) 的缺陷显著延长了虫的寿命.
- H3K4脱甲基酶RBR-2对于正常寿命至关重要,这表明过度的H3K4三甲基化是有害的.
- 延长寿命需要完整的成年生殖线和持续的卵子生产,ASH-2和RBR-2在生殖线内起作用.
结论:
- 在C. elegans中,ASH-2三体复合体,一种组分体H3 lysine 4三甲基转移酶,调节了C. elegans的寿命.
- H3K4甲基化/脱甲基化机械的生殖系特异性作用控制了人体长寿.
- 对衰老的表观遗传控制涉及通过基因组甲基化对染色质状态的生殖系调节.
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