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The Research Of Human 3D Genome Organization In Higher-resolution

Posted on:2021-03-16Degree:MasterType:Thesis
Country:ChinaCandidate:J S LiFull Text:PDF
GTID:2370330611497997Subject:Biology
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In the three-dimensional space of the nucleus,there are many chromatins spatial structures at different scales and levels that are be folded accurately by some chromatins to help the DNA regulatory elements realize the spaciotemporal specific expression regulation of related genes.Currently,the researches about the three-dimensional structure of chromatins has focused on large-scale structural changes,such as A / B compartments,the topologically associating domains(TADs)and chromatin loop domains,but the researches on the more detailed chromatin spatial structures within TADs has not been reported.This project is designed to identify the more detailed threedimensional structure of chromatins in human genome at high resolution by using relevant bioinformatics methods and SAFE Hi-C(simplified amplification-free and economically efficient Hi-C)technology that is based on the In situ Hi-C technology.And the K562 human cell line is the experimental materials.This project successfully constructed a high-quality SAFE Hi-C library.Compared with the published In situ Hi-C data,we found that the alignment of SAFE Hi-C and In situ Hi-C data are similar,both are over 91%,and the Hi-C contacts are 82.38% and 69.65%,intrachromosomal interactions are 81.08%,65.06%,respectively.The chromatin interaction map,decay curve and border index suggest that SAFE Hi-C data has more proximal chromatin interaction information.Secondly,we used Arrowhead algorithm to identify the TADs in SAFE Hi-C data and In situ Hi-C data,respectively,and found that proteins such as CTCF,RNA polymerase II,H3K27 ac and others are highly enriched in most TADs boundary,including SAFE Hi-C specific TADs boundary,In situ Hi-C data specific TADs boundary and common TADs boundary;In addition,by calculating the Border Index of SAFE Hi-C data and In situ Hi-C data,we successfully screened their borders,and found that the enrichment of CTCF,RNA polymerase II,H3K27 ac and other proteins in the two types of borders has no differences.By dividing the Border Index of SAFE HiC and In situ Hi-C,the different chromatin spatial interaction between them is further analyzed,and it is found that the border of SAFE Hi-C is higher than that of In situ Hi-C on the whole,and the proteins such as CTCF,RNA polymerase II,H3K27 ac had different enrichment degrees in the border regions of different ratios.
Keywords/Search Tags:gene expression regulation, three-dimensional genome, SAFE Hi-C technology, human three-dimensional genome fine structure
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