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Published 2 September 2003. doi:10.1083/jcb.200304096
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© The Rockefeller University Press, 0021-9525/2003/9/809 $5.00
The Journal of Cell Biology, Volume 162, Number 5, 809-820

Article

Inheritance of gene density–related higher order chromatin arrangements in normal and tumor cell nuclei



Marion Cremer1,3, Katrin Küpper1, Babett Wagler1, Leah Wizelman1, Johann v. Hase2, Yanina Weiland3, Ludwika Kreja4, Joachim Diebold5, Michael R. Speicher3 and Thomas Cremer1

1 Department of Biology II, Ludwig Maximilians University, 80333 Munich, Germany
2 Kirchhoff-Institute of Physics, University of Heidelberg, 69120 Heidelberg, Germany
3 Institute of Human Genetics, Technical University and GSF, 81675 Munich, Germany
4 Institute for Occupational, Social and Environmental Medicine, University of Ulm, 89070 Ulm, Germany
5 Institute of Pathology, University of Munich, 80337 Munich, Germany

Address correspondence to Marion Cremer, Dept. of Biology II, Chair of Anthropology and Human Genetics, University of Munich, Richard Wagnerstr. 10, 80333 Munich, Germany. Tel.: 49-89-2180-6713. Fax: 49-89-2180-6719. email: Marion.Cremer{at}lrz.uni-muenchen.de

A gene density–related difference in the radial arrangement of chromosome territories (CTs) was previously described for human lymphocyte nuclei with gene-poor CT #18 located toward the nuclear periphery and gene-dense CT #19 in the nuclear interior (Croft, J.A., J.M. Bridger, S. Boyle, P. Perry, P. Teague, and W.A. Bickmore. 1999. J. Cell Biol. 145:1119–1131). Here, we analyzed the radial distribution of chromosome 18 and 19 chromatin in six normal cell types and in eight tumor cell lines, some of them with imbalances and rearrangements of the two chromosomes. Our findings demonstrate that a significant difference in the radial distribution of #18 and #19 chromatin is a common feature of higher order chromatin architecture in both normal and malignant cell types. However, in seven of eight tumor cell lines, the difference was less pronounced compared with normal cell nuclei due to a higher fraction of nuclei showing an inverted CT position, i.e., a CT #18 located more internally than a CT #19. This observation emphasizes a partial loss of radial chromatin order in tumor cell nuclei.

Key Words: nuclear architecture; tumor cells; nuclear shape; chromosome territories; radial chromatin arrangement

Abbreviations used in this paper: 3D, three-dimensional; CGH, comparative genomic hybridization; CT, chromosome territory; GM-CFC, granulocyte-macrophage colony–forming cells; KS, Kolmogorov-Smirnov; MQ, median quartile.


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