Repetitive DNA sequences are genomic determinants for the 3D folding of metazoans genomes

The size of genomes exhibits a great variability despite a relatively similar number of protein coding genes. The increase in metazoan genomes sizes is partly due to the multiplication of repetitive DNA sequences. Despite their abundance, the role of these sequences remains largely unknown. It has been proposed that they might organize the 3D folding of genomes in nuclei and therefore play a role in the regulation of gene expression. To test this hypothesis we combined the most recent genome-wide Chromosomal Conformation Capture data together with genome annotations for the repetitive DNA sequences. We show that in human, mouse and drosophila, the genome is organized in a way that enables the specific co-localization of similar DNA repeats; few of which were already known to bridge distant parts of the genome. We finally show that the 3D organization of synteny blocs in mammalian nuclei is conserved in human and mouse. We propose that this can be explained by the enrichment of specific evolutionary related retrotransposons such as Alu and B1 in gene rich regions of the genomes. Taken all together, our results suggest a "functionalist" architectural role of repeated DNA sequences in the genome of higher eukaryotes.