Differences in the Localization and Morphology of Chromosomes in the Human Nucleus

doi:10.1083/jcb.145.6.1119

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© The Rockefeller University Press, 0021-9525/1999//1119 $5.00
The Journal of Cell Biology, Volume 145, Number 6, , 1999 1119-1131

Article

Differences in the Localization and Morphology of Chromosomes in the Human Nucleus

Jenny A. Croft, Joanna M. Bridger, Shelagh Boyle, Paul Perry, Peter Teague, and Wendy A. Bickmore

MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom

Using fluorescence in situ hybridization we show striking differencesin nuclear position, chromosome morphology, and interactionswith nuclear substructure for human chromosomes 18 and 19.Human chromosome 19 is shown to adopt a more internal positionin the nucleus than chromosome 18 and to be more extensivelyassociated with the nuclear matrix. The more peripheral localization of chromosome 18 is established early in the cell cycle andis maintained thereafter. We show that the preferential localizationof chromosomes 18 and 19 in the nucleus is reflected in theorientation of translocation chromosomes in the nucleus. Lastly,we show that the inhibition of transcription can have gross,but reversible, effects on chromosome architecture. Our datademonstrate that the distribution of genomic sequences betweenchromosomes has implications for nuclear structure and we discussour findings in relation to a model of the human nucleus thatis functionally compartmentalized.

Key Words: chromosome territories • genome organization • nuclear compartmentalization • transcription • translocations

Abbreviations used in this paper: 2D, two dimensional; 3D, three dimensional; AMD, actinomycin D; DAPI, 4,6-diamidino-2-phenylindole; DRB, 5,6-dichloro-β-D-ribofuranosylbenzimidazole; FISH, fluorescence in situ hybridization; HSA18, human chromosome 18; HSA19, human chromosome 19; MAA, 3:1 methanol/acetic acid; pFa, paraformaldehyde; PI, propidium iodide; TSA, Trichostatin A; Xa, active X chromosome; Xi, inactive X chromosome.

W.A. Bickmore is a Centennial Fellow in Human Genetics of the James S. McDonnell Foundation.

J.A. Croft and J.M. Bridger contributed equally to this work.

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