Evolution and function of chromatin domains across the tree of life

The genome of all organisms is spatially organized to function efficiently. The advent of genome-wide chromatin conformation capture (Hi-C) methods has revolutionized our ability to probe the three-dimensional (3D) organization of genomes across diverse species. In this Review, we compare 3D chromatin folding from bacteria and archaea to that in mammals and plants, focusing on topology at the level of gene regulatory domains. In doing so, we consider systematic similarities and differences that hint at the origin and evolution of spatial chromatin folding and its relation to gene activity. We discuss the universality of spatial chromatin domains in all kingdoms, each encompassing one to several genes. We also highlight differences between organisms and suggest that similar features in Hi-C matrices do not necessarily reflect the same biological process or function. Furthermore, we discuss the evolution of domain boundaries and boundary-forming proteins, which indicates that structural maintenance of chromosome (SMC) proteins and the transcription machinery are the ancestral sculptors of the genome. Architectural proteins such as CTCF serve as clade-specific determinants of genome organization. Finally, studies in many non-model organisms show that, despite the ancient origin of 3D chromatin folding and its intricate link to gene activity, evolution tolerates substantial changes in genome organization. Szalay et al. discuss cross-kingdom similarities and differences in 3D chromatin folding in relation to gene regulation, including in bacteria, archaea, mammals and plants. This comparison reveals certain factors as ancestral sculptors of the genome, but also that evolution tolerates considerable variety in genome organization.