四维细胞核体调控基因表达的数学理论

Mathematical theory of four-dimensional nucleome regulating gene expression

多尺度三维基因组结构驱动基因表达和细胞命运决定.尽管在一维线性基因组层面上的研究取得了显著进展,但三维空间基因组动态结构如何在功能上影响时空基因表达的变化仍不清楚.近年来,测序技术和影像技术的发展,使得四维核体基因组学的研究取得一系列进展.在本文中,讨论了三维基因组结构的多尺度性、其对基因表达的复杂调控以及时空动力学.接着对这一复杂的染色质结构动力学、表观修饰动力学和基因表达动力学进行理论建模,提出了可预测的多尺度耦合系统的建模框架.最后,讨论了未来关于四维核体动力学的研究方向.

The multiscale three-dimensional genome structure drives gene expression and cell-fate deci‐sion.Although significant progress has been made in the study of one-dimensional linear genomes,it is still unclear how the dynamic structure of three-dimensional spatial genomes affects spatiotemporal gene expression changes functionally.In recent years,the development of sequencing and imaging technologies has led to a series of advances in the study of four-dimensional nucleome genomics.In this review,we discuss the multiscale nature of the three-dimensional genome structure,its complex regulation of gene expression,and its spatiotemporal dynamics.Subsequently,we theoretically model this complex chromatin structure dynamics,epigenetic modification dynamics,and gene expression dynamics,and propose a predictive multiscale coupled modeling framework.Finally,we discuss fu‐ture research directions on four-dimensional nucleome dynamics.