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Published online January 14, 2008
doi:10.1083/jcb.200708204
The Journal of Cell Biology, Vol. 180, No. 1, 39-50
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Meaburn et al.
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Article

 Locus-specific and activity-independent gene repositioning during early tumorigenesis

Karen J. Meaburn and Tom Misteli

National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

Correspondence to T. Misteli: mistelit{at}mail.nih.gov

The mammalian genome is highly organized within the cell nucleus. The nuclear position of many genes and genomic regions changes during physiological processes such as proliferation, differentiation, and disease. It is unclear whether disease-associated positioning changes occur specifically or are part of more global genome reorganization events. Here, we have analyzed the spatial position of a defined set of cancer-associated genes in an established mammary epithelial three-dimensional cell culture model of the early stages of breast cancer. We find that the genome is globally reorganized during normal and tumorigenic epithelial differentiation. Systematic mapping of changes in spatial positioning of cancer-associated genes reveals gene-specific positioning behavior and we identify several genes that are specifically repositioned during tumorigenesis. Alterations of spatial positioning patterns during differentiation and tumorigenesis were unrelated to gene activity. Our results demonstrate the existence of activity-independent genome repositioning events in the early stages of tumor formation.

Abbreviations used in this paper: BAC, bacterial artificial chromosome; HSA, human chromosome; KS test, Kolmogorov-Smirnov test; MEC, mammary epithelial cell; NOR, nucleolar organizing region.


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