Human Molecular Genetics, 2001, Vol. 10, No. 3 211-219
© 2001 Oxford University Press
The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells
1MRC Human Genetics Unit, Crewe Road, Edinburgh EH4 2XU, UK and 2Randall Centre for the Molecular Mechanism of Cell Function, King’s College, Guy’s Campus, London SE1 1UL, UK
To fully understand genome function, the linear genome map must be integrated with a spatial map of chromosomes in the nucleus. Distinct nuclear addresses for a few human chromosomes have been described. Previously we have demonstrated that the gene-rich human chromosome 19 is located in a more central position in the nucleus than the similarly sized, but gene-poor, chromosome 18. To determine whether these two chromosomes are a paradigm for the organization of chromatin in the human nucleus, we have now analysed the nuclear organization of every human chromosome in diploid lymphoblasts and primary fibroblasts. We find that the most gene-rich chromosomes concentrate at the centre of the nucleus, whereas the more gene-poor chromosomes are located towards the nuclear periphery. In contrast, we find no significant relationship between chromosome size and position within the nucleus. Proteins 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 suggested that disruption of this organization may play a role in some disease pathologies. We show that the intranuclear organization of chromosomes is not altered in cells that lack the integral nuclear membrane protein emerin, from an individual with X-linked Emery–Dreifuss muscular dystrophy. This suggests that emerin is not necessary for localizing chromosomes at the nuclear periphery and that the muscular dystrophy phenotype in such individuals is not due to grossly altered nuclear organization of chromatin.
+ Present address: Department of Biological Sciences, Brunel University, Uxbridge, Middlesex UB8 3PH, UK
§ To whom correspondence should be addressed. Tel: +44 131 332 2471; Fax: +44 131 343 2620; Email: w.bickmore@hgu.mrc.ac.uk
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