Characterization Of The Chromatin 3D Conformation In Mouse Spermatogenesis And Clustering Analysis Of Topologicalling Associating Domains In MESC

The DNA in the cell nucleus is the blueprint that encodes all the genes and can decode into the proteins necessary for the function of the cells to sustain life.Under-standing the right way of information organization,storage and depackage in the cell nucleus is conducive to human health.Studies have found that changes in the informa-tion organization of chromatin conformation may lead to cancer and other diseases,and may also change the human body's response to infections such as viruses.This study mainly studies the three-dimensional conformational changes in mouse spermatogene-sis and the TADs(topological binding domains)types in embryonic stem cells.The first part of the paper is the study of the structure-function regulation of meiotic chromosomes by Hi-C and other omics techniques in mouse spermatogenesis across five stages.We demonstrated that chromatin loops are present prior to and after,but not at,the pachytene stage.By integrating Hi-C and RNA-seq data,we showed that the switching of A/B compartments between spermatogenic stages is tightly associated with meiosis-specific mRNAs and piRNAs expression.Moreover,our ATAC-seq data indicated that chromatin accessibility per se is not responsible for the TAD and loop diminishment at pachytene.Additionally,our ChIP-seq data demonstrated that CTCF and cohesin remain bound at TAD boundary regions throughout meiosis,suggesting that dynamic reorganization of TADs does not require CTCF and cohesin clearance.The second part of the thesis is the classification of topological binding domains.According to the transcription level of genes on the borders,the chromatin state of the borders' sequences,the size of TADs,and the first eigenvalues of the interaction matrix within the TADs,TADs are divided into nine categories.Type-SA TADs are found to be the most active and most conserved among cells;Type-A11 and Type-S22 TADs may be involved in stem cell differentiation and proliferation.In summary,this study supplements the understanding of the structure-activity re-lationship of the genome during mouse spermatogenesis,and particularly deepens the understanding of the commonalities and distinctions of chromatin conformations such as topological binding domains.