Organising Chaos: Domain Organization of Chromosomes in the Nucleus

Source: Guelen et al. (2008). Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453:948-951.

This is a great paper with interesting methods and exciting results. The authors use DamID to identify the regions of the genome that interact with the nuclear lamina (NL). For this they make a DNA adenine methyltransferase (Dam) fused to human lamin B1. Upon formation of the nuclear structure, Dam methylates the nearby adenine nucleotides that can be later identified as foci of interaction. Upon mapping genome-NL interactions (lamina associated domains or LADs) they compare the NL-free regions with those that are attached. Their first observation is that NL-bound regions have a low frequency of coding sequences, and those that are there are generally expressed at low levels. Secondly, NL-bound regions are isolated from the other parts of the genome through insulator proteins, promoters directed away from the LADs and GC boxes.

This paper makes the case for a complex level of chromosome organization where domains can be seperated by LADs and thus acting as perfect insulators.