show Abstracthide AbstractHere we describe the principles of 3D genome folding dynamics in vertebrates and show how lineage-specific patterns of genome reshuffling can result in different chromatin configurations. We (i) identified different patterns of chromosome folding across vertebrate species, (ii) reconstructed ancestral marsupial and afrotherian genomes analyzing whole-genome sequences of 10 species representative of the major therian phylogroups, (iii) detected lineage-specific chromosome rearrangements and (iv) identified the dynamics of the structural properties of genome reshuffling through therian evolution. Overall design: HiC of African elephant, aardvark, Tasmanian devil and tammar wallaby fibroblasts. H3K4me3 ChIP-seq of African elephant, aardvark, Tasmanian devil and tammar wallaby fibroblasts. CTCF ChIP-seq of African elephant, aardvark fibroblasts. RNA-seq of Tasmanian devil fibroblasts