Structure and function of the nucleus: anatomy and physiology of chromatin

A review of the literature accumulated recently on nuclear structure and function reveals that: (1) The nucleus is the interphase form of chromosomes (chromatin organizes and compartmentalizes the nucleus). (2) These organizational programs are morphogenetic in nature and are regulated by both DNA content and by epigenetic interactions. (3) In mammals with a diploid complement, it is very likely that chromosomes construct interphase domains based on their structural milieu (including any imprinted areas). These are the same structured areas that correspond to G- and R-bands with their varying DNA content and early versus late replication. (4) Changes in a position of a segment of DNA from one chromatin environment to another changes its availability to early replication factors and transcription factors as well as its nuclear positioning and chromatin architecture. This process was first described as positional effect variegation in Drosophila but is now found to be more general and explains many cases of direct clinical relevance. Examples in mammals include spreading of X inactivation, imprinting and changes in chromatin associated with chromosome translocation. (5) Chromosomal autoconstruction and reconstruction into a functional nucleus are altered during cell cycle and during differentiation (much more work needed on this area).