基因促进体的长距离相互作用景观
Amartya Sanyal1, Bryan R Lajoie, Gaurav Jain
1Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605-0103, USA.
Nature
|September 8, 2012
概括
这项研究使用5C绘制基因组相互作用图,揭示了调控元素和基因之间的复杂3D网络. 这些发现揭示了非编码DNA如何影响基因表达和疾病.
科学领域:
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 非编码的人类基因组包含功能元素和与疾病相关的变异.
- 控制调节元件和基因之间的相互作用的原则在很大程度上是未知的.
- 染色体循环与基因调节有关.
研究的目的:
- 综合地绘制人类基因组中转录起始点 (TSS) 和远端元素之间的相互作用.
- 了解这些远程基因组相互作用的规则及其在基因调节中的作用.
主要方法:
- 染色体构造捕获碳复制 (5C) 已应用于ENCODE试点区域.
- 为GM12878,K562和HeLa-S3细胞系生成了5C地图.
- 数据与ENCODE联盟数据集集集成.
主要成果:
- 每个细胞系发现了促进体和远部位 (增强体,促进体,CTCF结合位) 之间的1000多个长距离相互作用.
- 基因表达与促进剂-增强剂相互作用和增强剂RNAs相关.
- 相互作用显示上游偏差,经常被CTCF/凝聚素解锁,很少涉及最近的基因.
结论:
- 基因和调控元素形成复杂的3D网络,不仅仅是由基因组近距离决定的.
- 这些相互作用为了解基因调节和疾病机制提供了关键的背景.
- 这项研究揭示了对人类基因组三维组织的新见解.
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