基因组DNA在细胞核中并不是呈线性的一字排列,而是以三维结构高度折叠并浓缩成染色质的方式储存于核内,具有特定的高级空间结构和构象。高通量染色体构象捕获(high-througnput chromosome conformation capture, Hi-C)技术于2009年首次被提出,目前已得到大规模运用,使得人们对于三维基因组学有了更深刻的认识。研究表明,哺乳动物基因组三维层级结构单元由大到小依次为染色体疆域(chromosome territory, CT)、染色质区室(chromatin compartment A/B)、拓扑关联结构域(topological associated domain, TAD)和染色质环(chromatin loop),这些层级结构单元在基因转录和表达调控过程中发挥着重要作用。本文基于Hi-C技术从染色质的三维层级结构划分、构象单元作用以及三维基因组在发育、疾病等方面的应用进行阐述,旨在为更深入地了解哺乳动物三维基因组学研究提供参考。

Mammalian genomic DNA in the cell nucleus doesn’t exist in linear form but is highly folded and condensed into chromatin with a three-dimensional (3D) structure possessing a specific spatial structure and conformation. Hi-C, the high-throughput chromosome conformation capture technology, was first published in 2009, and it provides an in-depth view of 3D genomics. According to the size of DNA unit, the 3D hierarchical units of mammalian genome can be categorized sequentially as chromosome territory (CT), chromatin compartment A/B, topological associated domain (TAD), and chromatin loop. These hierarchical structural units play vital roles in gene transcription and regulation. In this review, we summarize the 3D hierarchical division of chromosomes, the effects of hierarchical units and the applications of Hi-C technology in development and disease. This review is intended to provide insights for the further study of 3D genomics in mammals.