通过核细胞间相互作用的剧烈损害解释表观遗传修饰的染色体展开:一个多层次的计算研究
Rosana Collepardo-Guevara1,2, Guillem Portella1,2, Michele Vendruscolo1
1†Chemistry Department, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW United Kingdom.
Journal of the American Chemical Society
|July 21, 2015
概括
体尾巴
科学领域:
- 结构生物学
- 表观遗传学
- 计算生物物理
背景情况:
- 基因尾巴和表观遗传修饰是基因表达和染色体结构的关键.
- 连接基因组尾巴与染色体状态的精确结构机制尚未完全理解.
- 染色体结构的实验性表征在技术上具有挑战性.
研究的目的:
- 阐明基因尾巴和氨酸乙化影响染色体折叠和基因调节的结构机制.
- 调查基因组尾巴的构造格局及其在染色质紧缩中的作用.
- 了解表观遗传修饰对分子层面上的染色质结构的影响.
主要方法:
- 多尺度计算建模,将二核酶体和基因组尾巴的原子分子动力学模拟与核酶体阵列的粗粒蒙特卡洛模拟相结合.
- 模拟在明确溶剂和离子中使用最先进的力场进行.
- 使用核磁共振 (NMR) 测量进行实验验证.
主要成果:
- 野生类型的体尾巴是灵活的和无序的.
- 素乙化显著增加了基因组尾巴中的二次结构顺序.
- 乙化通过减少纤维紧缩至关重要的尾巴相互作用来展开色素.
结论:
- 通过促进二次结构和减少核细胞间相互作用,素乙化改变了基因组的折叠.
- 这为表观遗传修饰如何影响色素结构和基因调节提供了分子解释.
- 多尺度方法为生物分子复杂动力学提供了新的见解.
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