The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells

To fully understand genome function, the linear genome map must be integrat ed with a spatial map of chromosomes in the nucleus, Distinct nuclear addre sses for a few human chromosomes have been described. Previously we have de monstrated that the gene-rich human chromosome 19 is located in a more cent ral position in the nucleus than the similarly sized, but gene-poor, chromo some 18, To determine whether these two chromosomes are a paradigm for the organization of chromatin in the human nucleus, we have now analysed the nu clear organization of every human chromosome in diploid lymphoblasts and pr imary fibroblasts. We find that the most gene-rich chromosomes concentrate at the centre of the nucleus, whereas the more gene-poor chromosomes are lo cated towards the nuclear periphery, In contrast, we find no significant re lationship between chromosome size and position within the nucleus, Protein s of the nuclear membrane or lamina are candidates for molecules that might anchor regions of the genome at the nuclear periphery and it has been sugg ested that disruption of this organization may play a role in some disease pathologies. We show that the intranuclear organization of chromosomes is n ot altered in cells that lack the integral nuclear membrane protein emerin, from an individual with X-linked Emery-Dreifuss muscular dystrophy, This s uggests that emerin is not necessary for localizing chromosomes at the nucl ear periphery and that the muscular dystrophy phenotype in such individuals is not due to grossly altered nuclear organization of chromatin.