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动态屏障调节凝聚力定位和基因组折叠在固定占用时

Hadi Rahmaninejad¹, Yao Xiao¹, Maxime M C Tortora¹

¹Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, USA.

bioRxiv : the preprint server for biology

|October 17, 2024

概括

基因组折叠依赖于凝聚力挤出DNA循环,由CTCF障碍物指导. 我们的动态模型表明,CTCF屏障结合时间,而不仅仅是占用,对基因组结构至关重要,与凝聚生命周期相匹配.

科学领域:

* 分子生物学 * 分子生物学
* 生物物理生物物理
* 基因组学是一个学科.

背景情况:

*哺乳动物基因组折叠涉及凝聚素介导的循环挤出,受到方向CTCF结合点的约束.
* CTCF站点作为障碍物,丰富凝聚力和定义拓关联域.
* 在染色体上,短CTCF居住时间和更长的凝聚性寿命之间存在差异.

研究的目的:

* 调查短暂的CTCF障碍是否可以解释观察到的基因组折叠特征.
* 开发一个包含CTCF约束/不约束利率的动态障碍模型.
*评估屏障动态对基因组和成像数据的影响.

主要方法:

* 开发了用于CTCF绑定和解绑的动态屏障模型.
*使用模型模拟了ChIP-seq,Hi-C和显微镜数据.
* 模型输出与实验生物物理测量结果进行比较.

主要成果:

* CTCF屏障结合时间与占用率一起,显著影响基因组折叠特征.
*CTCF边界与凝聚力挤出机寿命影响的比率模拟了ChIP-seq和Hi-C数据.
* 动态障碍是解释实验观察到的染色体形态变化的必要条件.

结论:

* CTCF屏障动态对于基因组折叠至关重要,而不仅仅是静态存在.
* 生物物理知情模型揭示了CTCF绑定时间接近凝聚生命周期.
* 整合蛋白质动态增强了对基因组折叠机制的理解.

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