中文摘要：

在细胞分裂间期,每条染色质都占据着特定的染色质领域（chromosome territory,CT）。每个CT领域内进一步分成不同的拓扑学相关区域（topological associated domain,TAD）,每个TAD又由若干子TAD（sub-TAD）构成。不同的TAD相互聚集,形成基因活跃表达和不表达的A、B两种组份或区室（compartment）。然而,目前对于染色质折叠方式及维持机制的研究尚无定论。核基质附着区（matrix attachment regions,MARs）是在不同物种基因组中广泛存在的一类富含AT序列的与核基质结合的DNA元件,能够通过与CTCF、SATB1等调控蛋白质相互作用,对远距离的基因表达进行调控。本研究以染色质三维结构为背景,通过整合染色质三维结构及组蛋白修饰等组学数据,对MARs元件与染色质三维结构的关系进行研究,对MARs元件参与形成的相互作用网络的结构及功能进行探索。结果发现,MARs元件与染色质三维结构高度相关,而且在高强度相互作用中占据较大的比例,提示MARs元件在染色质折叠方面发挥作用。此外,通过拓扑结构聚类分析还首次揭示,MARs元件分为不同类型,包括维持染色质领域及空间构象等的结构单元部分,以及调控基因表达等的功能单元部分。这表明,MARs元件在基因组三维高级结构的建立、维持以及功能等方面发挥重要作用。

英文摘要：

Chromatin,the largest single biological macromolecule of eukaryotes,is the common carrier of genetic and epigenetic information and stored in the nucleus as the basic existence form of genome.Relative to each other and radial nuclear positions,each chromatin is confined to a discrete region during the mitotic phase.This discrete but relative stable region is called chromosome territory.Each chromatin is folded into complex three dimensional structure（3D） of genome at different levels.The stable highorder structure of chromatin plays important roles in DNA replication,recombinant and transcription.As previously reported,function of many regulatory factors is dependent on the three dimensional space of chromatin structure.Matrix associated regions are widespread in difference species genomes,which areenriched with AT sequence and intensively interacted with nuclear matrix.It is closely connected with the nuclear skeleton in the cell nucleus,maintaining the structure of the nucleus.In order to explore the potential organization and function of matrix attachment regions（MARs）,particularly the relationship between MARs and three-dimensional structure of chromatin,Hi-C and other epigenomics datasets were integrated to perform the trans-omics analysis.The frequency distribution,network topological structure and biological functions of MARs were examined.The results revealed that MARs is highly correlated with the three-dimensional structure of genome,which strongly suggests that MARs might have important effect on the genome folding.Secondly,it was also shown that MARs could be categorized into different topological classes such as those of structure units to maintain chromatin loop and conformation,and also as functional units to regulate gene expression.These data indicated that MARs might exert important roles in the establishment,maintenance and regulation of genome 3D structure.