Abstract
Every living organism, from bacteria to humans, contains DNA encoding anything from a few hundred genes in intracellular parasites such as Mycoplasma, up to several tens of thousands in many higher organisms. The first observations indicating that the nucleus had some kind of organization were made over a hundred years ago. Understanding of its significance is both limited and aided by the development of techniques, in particular electron microscopy, fluorescence in situ hybridization, DamID and most recently HiC. As our knowledge about genome organization grows, it becomes apparent that the mechanisms are conserved in evolution, even if the individual players may vary. These mechanisms involve DNA binding proteins such as histones, and a number of architectural proteins, some of which are very much conserved, with some others having diversified and multiplied, acquiring specific regulatory functions. In this review we will look at the principles of genome organization in a hierarchical manner, from DNA packaging to higher order genome associations such as TADs, and the significance of radial positioning of genomic loci. We will then elaborate on the dynamics of genome organization during development, and how genome architecture plays an important role in cell fate determination. Finally, we will discuss how misregulation can be a factor in human disease.
Highlights
Over 60 years have passed since Watson and Crick published their famous model for the double helix structure of DNA
How this genome is packaged without compromising its accessibility when required is of interest to the entire field of molecular genetics, more so because congenital and developmental disorders are being linked to disruption of spatial genome organization
These loops are stabilized by CTCF, an architectural protein binding to the CCCTC motif, which is found at Topologically Associated Domains (TADs) boundaries (Rao et al, 2014; Figure 1)
Summary
Over 60 years have passed since Watson and Crick published their famous model for the double helix structure of DNA. Carl Rabl’s prediction of a preserved centromere-telomere orientation throughout the cell cycle and Boveri’s argument in favor of discrete “chromosome territories” based on his observations of blastomere nuclei of Ascaris megacephala, fueled the earliest ideas of functional compartmentalization of the nucleus (Rabl, 1885; Boveri, 1909). Both these observations were possible due to a combination of light microscopy advances that managed to achieve 1 μm resolution in the mid-1800s and the use of unique model organisms that enabled better distinction. Drawing inferences from various techniques, we take a look at the hierarchy of genome organization, starting with the lowest units building up toward higher-order structures (Figure 1)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
