Higher-Order Chromatin Organisation in Cell Nuclei: Structure and Function
Higher-order compartments of nuclear chromatin have been defined according to the replication timing, transcriptional activity, and information content. However, the compartments themselves are structured with some genetic loci near the centre of nucleus and the other near the periphery. Genetic loci are found in specific subregions of cell nuclei which form distinct layers at defined centre-of-nucleus to locus distances. Inside these layers, the genetic loci are distributed randomly. Some chromosomes are polarised with genes located in the inner parts of the nucleus and centromere located on the nuclear periphery; the polar organisation was not found for some other chromosomes. The internal structure of the higher-order compartments as well as the polar and non-polar organisation of chromosomes are basically conserved in different cell types and in various stages of the cell cycle. Some features of the nuclear structure are conserved even in differentiated cells and during cellular repair after irradiation, although shifted positioning of genetic loci was systematically observed during these processes. The structure of the cell nucleus is an important factor in the induction of chromosome aberrations. Exchange aberrations between two genetic loci are obviously less probable if the genetic loci are well separated from each other in the nucleus. On the other hand, if two genetic loci are superimposed in a small nuclear volume, the probability of exchange aberrations will be markedly increased. The nuclear higher-order structure is related also to the gene expression. Transcriptionally active regions are located in the inner parts of cell nuclei and the transition of some genetic loci to the nuclear periphery can be accompanied by the down-regulation of the locus. Epigenetic regulation of gene expression might be, therefore, an important additional mechanism in which gene silencing is hereditarily followed in subsequent generations.
S. Kozubek, E. Lukásová, E. Bártová, M. Kozubek, M. Skálníková, P. Jirsová, I. Koutná
Laboratory of Molecular Cytology and Cytometry,