The effect of translocation-induced nuclear reorganization on gene expression
- Louise Harewood1,5,
- Frédéric Schütz1,2,3,
- Shelagh Boyle4,
- Paul Perry4,
- Mauro Delorenzi2,3,
- Wendy A. Bickmore4 and
- Alexandre Reymond1,5
- 1 Center for Integrative Genomics, University of Lausanne, Lausanne CH-1015, Switzerland;
- 2 National Center of Competence in Research (NCCR) Molecular Oncology, Lausanne CH-1015, Switzerland;
- 3 Swiss Institute of Bioinformatics (SIB), Lausanne CH-1015, Switzerland;
- 4 Medical Research Council, Human Genetics Unit, Institute of Genetics and Molecular, Medicine, Edinburgh EH4 2XU, United Kingdom
Abstract
Translocations are known to affect the expression of genes at the breakpoints and, in the case of unbalanced translocations, alter the gene copy number. However, a comprehensive understanding of the functional impact of this class of variation is lacking. Here, we have studied the effect of balanced chromosomal rearrangements on gene expression by comparing the transcriptomes of cell lines from controls and individuals with the t(11;22)(q23;q11) translocation. The number of differentially expressed transcripts between translocation-carrying and control cohorts is significantly higher than that observed between control samples alone, suggesting that balanced rearrangements have a greater effect on gene expression than normal variation. Many of the affected genes are located along the length of the derived chromosome 11. We show that this chromosome is concomitantly altered in its spatial organization, occupying a more central position in the nucleus than its nonrearranged counterpart. Derivative 22-mapping chromosome 22 genes, on the other hand, remain in their usual environment. Our results are consistent with recent studies that experimentally altered nuclear organization, and indicated that nuclear position plays a functional role in regulating the expression of some genes in mammalian cells. Our study suggests that chromosomal translocations can result in hitherto unforeseen, large-scale changes in gene expression that are the consequence of alterations in normal chromosome territory positioning. This has consequences for the patterns of gene expression change seen during tumorigenesis-associated genome instability and during the karyotype changes that lead to speciation.
Footnotes
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↵5 Corresponding authors.
E-mail Louise.Harewood{at}unil.ch.
E-mail Alexandre.Reymond{at}unil.ch.
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[Supplemental material is available online at http://www.genome.org. The gene expression data from this study have been submitted to the NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo) under series accession no. GSE13122.]
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Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.103622.109.
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- Received November 26, 2009.
- Accepted March 4, 2010.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press