影响染色体三维结构的主要因素及其研究进展

The impact factors of 3D genome organization

染色体的三维结构与基因表达的精准调控密切相关,染色体空间结构的改变也常会影响细胞中多种生物学活动的有序进行.近年来,染色质空间构象捕获技术和测序技术的发展,使得三维基因组学的研究取得一系列进展.科学家们发现,染色质逐级折叠压缩,具有严密的层级结构,而影响染色质三维结构的因素则涉及DNA序列和蛋白复合体等多个方面.本文综述了影响三维基因组结构的主要因素,包括一维基因组层面上的DNA序列及其共价修饰、与基因结构以及顺式调控元件相互作用的蛋白复合体、核小体排布与组蛋白修饰以及在有丝分裂和染色体多倍化等过程中特有的三维结构变化等多个方面.通过总结这些因素如何影响染色体的三维结构以及相关的研究现状,揭示了染色体三维结构研究的重要作用.本文还简要总结了三维基因组学研究所面临的主要问题,并据此展望该领域将来的主要研究方向和可能的应用前景.

The 3 D architecture of chromosomes is involved in the precision regulation of gene expression, and the changes in spatial conformation of chromosomes, accordingly, influence the biological processes in a cell. Recent findings in 3 D genomics, through technological advances in approaches combining chromosome conformation capture(3 C) and DNA sequencing, have greatly improved our understanding that how the chromatin is folded. The chromosomes are tightly packed in the nucleus with hierarchical structural units, and these units are influenced by many factors such as DNA sequence itself and the associated protein complex. In this review, we focus on the major impact factors of 3 D genome organization, including the primary DNA sequences and the covalent modification of DNA(e.g. methylation);the protein complexes interplaying with gene structures and cis regulatory elements;nucleosome positioning and histone modifications;and how the structure of 3 D genome changes in mitosis and polyploidization. We highlight the importance of 3 D genome research by summarizing the current situation and progresses in studies of the impact factors of chromatin structure. We also discuss the critical challenges in the field, and propose the future directions as well as the potential applications in diseases.