起航三维基因组学研究

Emergence of 3D genomics

人类基因组测序完成已有十多年.但是,基因组信息如何指导基因在特定空间和时间表达的机理仍有待阐明."结构决定功能"是认识自然规律中的一个共识.在生物学中,这一共识不仅适用于RNA、蛋白质等小规模的有机分子,同样也应该适用于全基因组这样的DNA大分子.最近的研究表明,基因组的三维空间结构对基因组的表达、调控等功能有重要的影响.因此,研究全基因组的三维空间结构和功能成为基因组学一个新发展趋势.基因组三维空间结构与功能的研究简称三维基因组学,是指在考虑基因组序列、基因结构及其调控元件的同时,对基因组序列在细胞核内的三维空间结构,及其对基因转录、复制、修复和调控等生物过程中功能的研究.随着大规模基因组测序技术的发展,我们已经拥有研究三维基因组的相关技术如ChIA-PET和Hi-C.初步的ChIA-PET和Hi-C数据分析展示了基因组三维空间结构对基因组功能的意义,为进一步研究基因组三维空间结构和功能提供了基础.本文总结了三维基因组学研究的发展,概括了三维基因组学研究中的问题和目前的进展,并讨论了可能的应用前景.登高更见远,期待三维基因组学研究将深化对生命现象和规律的认识,为基础生物学发展带来新契机、为更进一步推动生物医学及农业应用打下坚实的基础.

It is already more than 10 years after the completion of Human Genome Project. However, the mechanism about how genomic information guides the gene expression in a particular space and time remains to be elucidated. ＂Structure determines function＂ is a consensus that we understand the laws of nature. In biology, this consensus is not only applicable to RNA, protein and other small-scale organic molecules; the same should also apply to macromolecules such as the entire DNA composition of the whole genome. Recent studies have shown that three-dimensional （3D） structure of the genome has an important impact on the regulation of gene transcription and other nuclear functions. Therefore, the study of the 3D structure and function of the whole genome （referred to as 3D genomics） has become a new trend of development in genomics. With the consideration of the genome sequence, gene structure and regulatory elements at the same time, 3D genomics studies the 3D structure of the genome in the nucleus, and its impact on gene transcription, replication, repair, regulation and others biological processes. With the progress of large-scale genome sequencing technology, we already have the relevant technologies such as ChlA-PET and Hi-C for the study of 3D genomics. Preliminary results showed the influence of genome 3D structures to genome functions, which provides the basis for further study of genome structure and function in the spatial nuclear space. This paper summarizes the emergence of 3D genomics, lists the issues and the current progress in this new field, and discusses possible applications of 3D genomics to human health and agriculture researches. We anticipate that 3D genomics will provide novel insights into the genome regulatory functions and provide new opportunities of improving human life qualities.