Our genome is not linear. Nope, it’s a three-dimensional labyrinth of regulatory nooks and crannies . Gibcus and Dekker recently published this free review that looks at the spatial hierarchy of genomic organization and how it modulates gene expression. This is a great resource for those of you looking to beef up your understanding of chromosome architecture and the interactions that exist within it.
Key concepts reviewed include:
Chromosomes are not able to physically move through the nucleus and are thus restricted to their respective chromosome territories (CTs). Thus, loci located on the same chromosome interact more frequently than loci located on different chromosomes. However, nuclear lamina (CL), located on the inside of the nuclear envelope, can anchor long stretches of chromatin to allow distant loci to connect in 3D space.
Compartmentalization by Association
Topologically associating domains, or TADs, are characterized by frequent long-range associations of loci in the same domain but less frequent associations of loci in adjacent domains. TADs thus compartmentalize genomes into discrete domains.
Connecting Genes and Regulatory Elements in 3D space
The best-studied long-range interactions are those between genes and distal regulatory elements, such as enhancers. Such long-range interactions are made possible by looping out intervening DNA and allowing gene regulatory elements to interact with promoters through direct protein interactions, as demonstrated for the â-globin locus.
Spatial Genomic Connectivity
Genes can interact with more than one distal element, and each distal element can interact with more than one gene, thus creating a very complex three-dimensional regulatory network. Furthermore, the authors propose that TADs are the chromosomal structures that ensure robust long-range gene regulation in every cell.
Check out this great, free review that’s packed with useful information and historical info.
The Hierarchy of the 3D Genome
Johan H. Gibcus and Job Dekker
Cell, Volume 49, Issue 5, 773-782, 7 March 2013