Genes are expressed (red) from varying sites in chromosome territories (green).

In the first direct comparison between the spatial organization of a region of the human genome with the syntenic region in the mouse, Mahy et al. report on page 579 that genes are not preferentially localized to the periphery of chromosome territories. The results contradict earlier analyses of nuclear organization, and suggest that a popular model correlating chromosome territory organization with transcriptional activity may need to be revised.

Previous studies have suggested that genes lie on the chromosome territory periphery, whereas intergenic sequences occupy the interior of the territory. According to the inter-chromosome domain (ICD) model, this is because the higher order structure of the territory blocks access by the transcriptional machinery. The authors compared the spatial organization of a 1-Mb stretch of the human genome and the syntenic murine sequence, and found that although there is a conserved spatial organization within these territories, genes in these segments do not preferentially localize to the periphery. Using cell lines with different gene expression patterns, Mahy et al. also saw no differences in the intraterritory positions of expressed and repressed genes, suggesting that the transcriptional machinery can reach genes without gross remodeling of chromosomal territories. ▪