Location of dCNEs in the vicinity of homeobox paralogs ISL1 (Chr5) and ISL2 (Chr15). ISL1 and ISL2 are the only paralogs within 1.5 Mb of the dCNEs (represented by green boxes) present in both regions (full extent not shown). The dCNE on Chr5 is located within a ‘gene desert’ and is ∼926 Kb 3′ of the ISL1 translation start site. In a similar manner to 27 other dCNE families (Supplemental Table S2), one dCNE is located within the intron of a gene (in this case ZNF291) while the other is located in a large intergenic region (spanning 1.39 Mb between ISL1 and PELO). In isolation, we would normally presume the dCNE on Chr15 to be associated with ZNF291, the closest trans-dev gene. However, as ZNF291 has no paralogs in the human genome, the ISL paralogs are far more likely to be the true associated genes of the dCNEs. In addition, this dCNE family has undergone an inversion event so that one dCNE is located in the same orientation to the target gene in one instance and the opposite orientation to the target gene in the other. Diagram adapted from the Ensembl Genome Browser (Hubbard et al. 2005).
