核体,DNA结合蛋白和DNA序列调节逆转录病毒整合目标点选择
1Department of Biochemistry and Biophysics, University of California, San Francisco 94143.
Cell
|May 29, 1992
概括
复原病毒DNA整合到染色质中显示了序列偏差,并且更喜欢核细胞上暴露的DNA. 染色体结构影响了融合部位的选择,而蛋白质阻断了接入.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 复原病毒DNA整合是复原病毒复制的一个关键步骤.
- 了解整合部位选择对于理解病毒病原和基因治疗至关重要.
- 染色体结构,DNA和蛋白质的复合体,显著影响DNA相关的细胞过程.
研究的目的:
- 为了研究逆转录病毒DNA整合点在裸体DNA和染色质中的精确分布.
- 确定DNA序列和染色质结构对整合部位偏好的影响.
- 为了比较由不同的病毒整合酶介导的点选择机制.
主要方法:
- 开发和应用一种基于聚合酶链反应 (PCR) 的新型检测方法.
- 在裸体DNA目标中分析集成位点分布.
- 在组装的染色体内和微染色体上的整合模式的调查.
主要成果:
- 整合到裸体DNA中显示不均的分布,表明特定序列偏好.
- 在染色体中,整合有利于核细胞DNA螺旋上暴露的主要沟的部位,显示10bp的周期性.
- 染色体组装增加了许多位点的反应性,集成在核体区域更频繁地发生.
- 在被特定位点的DNA结合蛋白占据的区域中抑制了整合.
- 不同的病毒核蛋白复合体和整合酶表现出不同的目标部位选择.
结论:
- 复原病毒DNA整合受到内在DNA序列特性和染色质的更高阶结构的影响.
- 核位定位和DNA可访问性是整合地点偏好的关键决定因素.
- 集成机制本身在决定集成发生在哪里发挥着作用,突出显示了这个过程的复杂性.
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