Year: 2026
Type: preprint
Abstract: Chromosome was "self-assembled" into a complex three-dimensional topology in the nucleus, which provided the structural basis for important biological processes such as gene expression regulation and cell differentiation. The current understanding of the three-dimensional organization of the genome is based on high-throughput sequencing and imaging technologies to visualize the conformation of chromatin in its native environment. This study proposes a new research perspective and technical means to use fusion genes to determine the interaction information and three-dimensional structure of chromosomes. This three-dimensional information provided by the fusion gene spectrum not only shows the universality of the spatial layout of chromosomes, but also increases the interpretability of the occurrence of fusion genes. The chromatin conformation capture data of multiple tissues and periods is significantly correlated with the strength of fusion genes. For example, the frequency of trans-interaction between chromosomes 11 and 17 was the highest, and the frequency of fusion gene occurrence corresponding to KMT2A on chromosome 11 was the highest. Therefore, we infer that this structural universality is a common feature of the human genome, which provides a theoretical basis and data for predicting chromosome fusion events. Significance Three-dimensional organization of chromosomes is significant for understanding the biological processes, currently, the understanding of the structure of chromosomes and its underlying mechanisms is still largely limited. Here, we determined the sharing pattern of spatial organization through chromosomal translocation data in malignant tumors of multiple tissues and periods. The three-dimensional structure indicated that chromosome 1 was close to the nucleolus, while chromosome 20 was distributed on the periphery. High density of SD sequences near the fusion gene loci and the small difference in GC content between fusion gene pairs were the key factors promoting the formation of fusion genes. This work reveals the causes of fusion genes at the molecular level and maps the universal three-dimensional spatial structure of chromosomes.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7221097168