早期营养调节小鼠特定rDNA遗传变异的表观遗传状态
Michelle L Holland1, Robert Lowe2, Paul W Caton3
1The Blizard Institute, Barts, and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK. m.holland@qmul.ac.uk v.rakyan@qmul.ac.uk.
Science (New York, N.Y.)
|July 9, 2016
概括
早期的营养通过表观遗传变化影响终身健康. 在小鼠中的蛋白质限制改变了核糖体DNA (rDNA) 的甲基化,将生长与表观遗传联系起来.
科学领域:
- 表观遗传学
- 发育生物学
- 营养科学
背景情况:
- 早期的环境因素,如营养不良或怀孕期间的压力,可以显著改变后代的终身健康结果.
- 假设表观遗传机制是这些长期影响的关键调解者,弥合环境暴露和表型变化.
研究的目的:
- 调查早期营养侮辱对表观遗传修饰的影响.
- 确定特定的基因组区域和机制,以调解不理想的早期环境对后代表型的影响.
- 探索遗传变异在环境诱导的表观遗传反应中的作用.
主要方法:
- 从受孕到断奶期间,小鼠接受了蛋白质限制.
- 对核糖体DNA (rDNA) 的DNA甲基化水平进行了分析,并与生长限制相关联.
- 在成年期检查表观遗传反应,重点关注特定的rDNA遗传变异.
- 还评估了母亲的高脂肪和肥胖饮食的影响.
主要成果:
- 在早期发育期间的蛋白质限制导致了生长限制和rDNA甲基化之间的线性相关性.
- 这种由环境引起的表观遗传变化持续到成年.
- 表观遗传反应是针对促进体区域中具有特定遗传变异的rDNA副本.
- 在暴露于母亲高脂肪或肥胖饮食的后代中观察到类似的表观遗传效应.
结论:
- 早期的营养侮辱可能导致持续的表观遗传修饰,特别是rDNA的DNA甲基化.
- 这些环境诱导的表观遗传变化受到潜在的遗传变异的影响.
- 核糖体DNA (rDNA) 被确定为营养侮辱的关键基因组标,介导终身的表型效应.
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