The effect of translocation-induced nuclear reorganization on gene expression

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.

Copy number variation modifies expression time courses

“…(Merla et al 2006;Guryev et al 2008;Cahan et al 2009;Henrichsen et al 2009b). Interestingly, recent results have shown that structural variants can have an effect on normal copy number genes positioned along the entire length of a chromosome (Harewood et al 2010;Ricard et al 2010). Our analyses also corroborate the finding that genes within CNVs have particular properties with respect to their spatial expression patterns and dosage sensitivity (Henrichsen et al 2009b).…”

The actin family member Arp6 and the histone variant H2A.Z are required for spatial positioning of chromatin in chicken cell nuclei.

“…Recent observations indicate that the radial distribution of CTs affects the expression of a number of genes, but does not necessarily correlate with gene expression (Harewood et al, 2010;Küpper et al, 2007;Meaburn and Misteli, 2008). Similar results were obtained in 'tethering' experiments (Kumaran and Spector, 2008;Reddy et al, 2008).…”

Genome Structures and Transcriptomes Signify Niche Adaptation for the Multiple-Ion-Tolerant Extremophyte Schrenkiella parvula

“…"copy-neutral" structural variants) can affect gene expression as well, either by changing regulatory elements or creating positional effects (Harewood et al, 2010(Harewood et al, , 2012Haraksingh and Snyder, 2013). Homologous genes involved in structural variations between the genomes of S. parvula and Arabidopsis contained more divergent promoters (Fig.…”