An overview of hierarchical organization of eukaryotic genome. Genome is hierarchically packed into a tiny nucleus at different scales: chromosome territories, compartments, topologically associating domains (TADs), loop domains, and long-range enhancer-promoter contacts. Chromosomes occupy their own preferential location in the nucleus (multiple colors), referred to as territories. Each territory consists of two compartments: A and B. A compartment (light yellow) is composed of active epigenetic marks and actively transcribed genes, and associated with nuclear speckles (red circles). Repressive epigenetic marks and inactive genes constitute the B compartment (light blue), located close to the nuclear lamina (yellow and red wavy lines) and nucleolus (black circle). TADs are defined as highly self-interacting domains with the boundaries demarcated by CCCTC-binding factors (CTCFs) (light red) with cohesin complex (blue) (middle square). CTCF and cohesin (blue) play an important role in loop extrusion mechanism. At the finest scale of genome folding, long-range enhancer-promoter contacts are mediated by multiple different factors such as transcription factors (blue-green), YY1 (salmon), mediators (green), RNA polymerase II (pink) and non-coding RNAs (wavy brown lines) that promote contacts between cis-regulatory elements (CREs) (light yellow and orange square representing enhancer and promoter, respectively) (right square). The size of each scale ranges from 1 to 100 Mb for territories and compartments, 40 kb to 3 Mb for TADs and loop domains, and from 1 kb to few Mb for long-range enhancer-promoter contacts.
