邻近的TAD之间的绝缘由它们边界的宽度通过不同的机制控制
Andrea Papale1, Julie Segueni2, Hanae El Maroufi2
1Department of Biology, Computational Biology and Applied Mathematics, Ecole Normale Supérieure, Institute of Biology at Ecole normale Superieure, Université Paris Sciences et Lettres, Paris 75005, France.
拓关联域 (TADs) 是由边界分隔的基因组区域. 更广泛的TAD边界更有效地阻止相互作用,增强基因组组织和转录调节.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 计算生物学 计算生物学
背景情况:
- 拓关联域 (TADs) 对于基因组组织至关重要,它定义了具有明显交互配置文件的子Megabase区域.
- 众所周知,TAD边界通常富含CTCF结合位点 (CBS),可以限制增强剂-促进剂相互作用并阻止循环挤出.
- 控制TAD边界形成的机制及其在基因组架构中的确切作用仍然不完全理解.
研究的目的:
- 调查TAD边界宽度,组成和绝缘效率之间的关系.
- 探索不同的边界配置如何影响基因组组织和转录调节.
- 阐明扩展的TAD边界在抵消虚假的TAD间接触中的作用.
主要方法:
- 基于宽度和CTCF结合位点分布的TAD边界的全基因组分类.
- 修改随机交联聚合物模型以模拟TAD绝缘的边界效应.
- 对Hi-C数据的分析,以验证有关TAD间联系的计算预测.
主要成果:
- TAD边界宽度存在于连续体上,与CBS分布,色素特征和调节元素相关.
- 边界宽度对TAD绝缘有不同的影响,影响局部和远部相互作用.
- 增加边界宽度被证明可以减少远程TAD间接触,与Hi-C数据一致.
- 扩展边界有效地抵消循环挤出阻断促进邻近TADs的虚假混合.
结论:
- TAD边界宽度是基因组组织和增强剂-促进剂相互作用特异性的关键决定因素.
- 更宽的TAD边界提高了循环挤出阻断的效率,从而保持了不同的监管环境.
- TAD边界宽度通过调节跨基因组域的远程联系,提供了一个额外的转录调节层.
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