Meeting Abstract
We sought to find how spatial organisation allowed for evolution of increased complexity of gene regulation by comparing the genome 3D organization of species from different clades using chromosome conformation capture techniques. We developed a set of computational tools to identify features associated with TADs and compartments and showed that the characteristic features of loop-extrusion domains are far less prominent in protostomes (such as Drosophila melanogaster) than in vertebrates. Accordingly, the drosophila genome appears mostly folded in small compartments, reflecting the nature of the underlying chromatin and transcriptional activity. In contrast, the domains we observed in the hemichordate S. kowaleskii and in the lancelet showed features characteristic of loop-extrusion and their boundaries showed significant and strong enrichment for CTCF motifs, indicating that they correspond predominantly to bona fide TADs. Furthermore, by using single-cell RNA-Seq data, we show that in hemichordates, genes located in TADs are more likely co-regulated than genes separated by a TAD boundary. We did not observe such domains in cnidarians, who branched before the evolution of CTCF, or tunicates, such as Ciona intestinalis, who has a modified CTCF gene, suggesting that they use different systems for gene regulation. Altogether, our studies underline that the evolution of the 3D genome, and in particular the innovation represented by cohesin-based and CTCF-delimited TADs, may have fueled regulatory innovation by extending the possible genomic space available to store gene regulatory elements.
