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.

Increasing evidence indicates that non-DNA sequence-based epigenetic information can be inherited across several generations in organisms ranging from yeast to plants to humans. This raises the possibility of heritable ‘epimutations’ contributing to heritable phenotypic variation and thus to evolution. Recent work has shed light on both the signals that underpin these epimutations, including DNA methylation, histone modifications and non-coding RNAs, and the mechanisms by which they are transmitted across generations at the molecular level. These mechanisms can vary greatly among species and have a more limited effect in mammals than in plants and other animal species. Nevertheless, common principles are emerging, with transmission occurring either via direct replicative mechanisms or indirect reconstruction of the signal in subsequent generations. As these processes become clearer we continue to improve our understanding of the distinctive features and relative contribution of DNA sequence and epigenetic variation to heritable differences in phenotype.

https://www.youtube.com/watch?v=Pl44JjA--2k&t=8s Synopsis of the YouTube video: this short video recapitulates our current understanding of genome organization in the three-dimensional space of the cell nucleus, starting from nucleosomes, which wrap 146 base pairs of DNA, all the way to entire chromosome territories that may contain hundreds of million base pairs of DNA sequence. In-between these two extremes, the hierarchical folding of the chromatin fiber into “nucleosome clutches”, “chromatin nanodomains or CNDs”, “Topologically Associating Domains or TADs” (including their mechanism of formation via loop-extrusion) and the “A and B compartments” are presented. We include below references that support and supplement what is described in our video. We stress that some of the mechanisms involved in 3D genome organization are still debated in this research field. We also include below additional videos on the subject. Enjoy the video!