由Chd1染色体重塑器进行的双向核细胞滑动整合了内在依赖序列和依赖ATP的核细胞定位
Sangwoo Park1, Giovanni B Brandani2, Taekjip Ha1,3,4
1Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Nucleic acids research
|September 22, 2023
概括
像Chd1这样的染色体重塑器可以通过滑动DNA来定位核体,优先将序列变异定位在特定位置附近. 这种DNA滑动机制影响这些重塑器如何与DNA扰动相互作用.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 生物化学 生物化学
背景情况:
- 染色体重塑器是调节DNA可访问性的基本分子机器.
- 这些酶利用一个ATPase电机来移动DNA相对于基因质核.
- 核体定位中的依赖序列偏差表明DNA序列影响重塑器活动.
研究的目的:
- 为了研究Chd1染色体重塑器的核细胞定位如何受到局部DNA扰动的影响.
- 了解Chd1与DNA相互作用并定位具有序列变异的机制.
主要方法:
- 利用特定地点的DNA裂变测试与下一代测序相结合.
- 通过Chd1在Widom 601和自然的+1核序列上检查核位.
- 采用计算建模来解释观察到的DNA扰动局部化.
主要成果:
- Chd1偏偏局部化的DNA扰动 (例如,多A:dT) 段,不匹配,插入) 距离其运动结合部位 (SHL2) 大约一个螺旋转.
- 这种局部化发生在工程和自然核细胞定位序列上.
- 建模表明,这种现象是由于改造器的双向DNA滑动引起的.
结论:
- 核细胞附近的DNA扰动可以通过滑动机制被Chd1积极重新定位.
- DNA扰动的定位受改造者的运动域位置和DNA序列的影响.
- 通过强核位定位序列,DNA扰动的屏障效应可以被放大.
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