Ultraconserved elements occupy specific arenas of three-dimensional mammalian genome organization

Abstract

This study explores the relationships between three-dimensional genome organization and the ultraconserved elements (UCEs), an enigmatic set of DNA elements that show very high DNA sequence conservation between vertebrate reference genomes. Examining both human and mouse genomes, we interrogate the relationship of UCEs to three features of chromosome organization derived from Hi-C studies. Firstly, we report that UCEs are enriched within contact domains and, further, that the UCEs that fall into domains shared across diverse cell types are linked to kidney-related and neuronal processes. In boundaries, UCEs are generally depleted, with those that do overlap boundaries being overrepresented in exonic UCEs. Regarding loop anchors, UCEs are neither over- nor under-represented, with those present in loop anchors being enriched for splice sites compared to all UCEs. Finally, as all of the relationships we observed between UCEs and genomic features are conserved in the mouse genome, our findings suggest that UCEs contribute to interspecies conservation of genome organization and, thus, genome stability.