Study On Method Of Chromatin Dynamics Based On Hi-C

Higher-order chromatin structure that exists in eukaryotic nucleus realizes not only the assembling and packaging for genomic DNA but a way of regulating gene expression.It presents a dynamic form and varies in different cell status and types.Hi-C technology is able to capture chromatin interactions in the whole genome.This paper focuses on the three aspects:1,characteristics of the chromatin multiple interactions and their changes in differentiation,which means to analyze the interactions(close contacts)among multiple chromatin fragments(n?3)and their changes in different types of cells.2,visualization of chromatin interaction,that is to use a model to directly show the chromatin interacton information,which is determined by Hi-C.3,the biological significance of chromatin multiple interactions and chromatin structure dynamics.With the Hi-C data of human embryonic stem cells and four differentiated cells,the chromatin multiple interaction sites(regions)were identified using two genomic loci of each Hi-C Read,and the chromatin interaction networks were constructed by the depth-first traversal algorithm.We found that chromatin multiple interaction accounted for?30%of total interactions,and show a feature of local enrichment.Number of the multiple interaction sites is more in stem cells than in differentiated cells.The chromatin interaction networks had star shape motif.The concentration degree of the networkis was different across the cell lines in some local regions,but similar in overall concentration.The stem cells and the differentiated cells shared 70%?80%genes associated with chromatin interactions,and these common genes were active in expression.In short,chromatin multiple interactions remained stable as a whole with local changes in differentiation.Based on the Hi-C data,the three-dimensional structure model of chromatin and the visualization method of chromatin spatial structure were constructed through multi-dimensional scaling(MDS)algorithm.The characteristics of three-dimensional structure were analyzed by combining with gene expression and epigenetic information.The results showed that the model is able to directly show the spatial interactions(close contacts)of chromatin based on Hi-C information.Among the different types of cells,the average distance between adjacent chromatin sites varied dramatically,while the direction angle changed slightly,indicating that chromatin dynamics involved more in translational movement rather than rotation or distortion.More than 50%of chromatin structure was conservative(r>0.8)in the stem cells and the differentiated cells,and the linear position of the conservative region was relatively fixed.Epigenetic modifications mainly occurred on the genomic regons where the chromatin structure is not conservative and the structures are close to each other.In short,the differentiation-realted chromatin change mainly involed distance translation and epigenetic modifications.Taken together,In this paper,based on Hi-C data,the chromatin structure characteristics was studied through analysizing the chromatin multiple interactions and constructing the visualization model The results suggested that the chromatin multiple interaction occupied a high proportion and the proportion decreased during differentiation;The chromatin dynamics,dominated by translation,associated with the epigenetic modifications,mainly occurred in the tight interaction regions.The methods and results of this paper provided clues for understanding the chromatin structure and its changes.