核细胞位和聚合物力学解释了100kbp尺度上的基因组接触
John Corrette1, Jiachun Li2, Hanjuan Shao2
1Mathematical, Computational and Systems Biology, University of California Irvine.
bioRxiv : the preprint server for biology
|October 10, 2024
概括
基因组的3D组织和基因表达受核素定位的影响. 生物物理模型显示,基因之间的核体解释了71%的DNA接触,突出了它们在基因调节中的作用.
科学领域:
- 基因组学就是基因组学.
- 生物物理学的生物物理.
- 分子生物学分子生物学
背景情况:
- 基因组的3D组织对于调节基因表达至关重要.
- 核细胞,DNA围绕着基因组蛋白包裹,影响DNA机制和基因组组织.
- 核细胞定位对DNA接触的影响和聚合物力学作用仍然不清楚.
研究的目的:
- 研究基因位点之间的核细胞定位如何影响DNA接触.
- 确定聚合物力学在多大程度上解释了这些DNA接触.
- 开发一个生物物理模型,整合核细胞定位和DNA机制.
主要方法:
- 开发了一种染色体DNA的随机聚合物力学模型,其中包含核细胞诱导的扭曲和包裹.
- 结合的ATAC-seq数据用于可访问区域的核细胞定位,使用电子显微镜用于在低可访问区域的间距.
- 将模型应用于巨细胞中的炎症基因 (IL6,IL15,CXCL9,CXCL10) 并将预测与4C-seq接触数据进行比较.
主要成果:
- 聚合物力学,包括核位定位,解释了在500千基基对区域内的71%的密切DNA接触.
- 核细胞的位置,不仅仅是数量,显著影响DNA接触.
- 该模型准确地预测了4C-seq实验测量的接触.
结论:
- 基因组接触在千倍基对尺度是多因素的,但在很大程度上可以通过物理机制来解释.
- 核体在调解DNA接触方面发挥着至关重要的作用,无论是在基因位置还是在基因位置之间.
- 开发的方法可以评估活跃的基因调节,并建议基因功能与聚合物力学依赖的调节机制进化.
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