text: One study focused on a regulatory archipelago, a region with “islands” of coding sequences surrounded by vast noncoding regions. The study, which explored the effects of regulation on the hox genes, initially focused on two enhancer sequences, GCR and Prox, which are located 200 basepairs and 50 basepairs respectively upstream of the Hox D locus. To manipulate the region, the study inverted the two enhancer sequences and discovered no major effects on the transcription of the Hox D gene, even though the two sequences were the closest sequences to the gene. Thus, the turned to the gene desert that flanked the GCR sequence upstream and found 5 regulatory islands within it that could regulate the gene. To select the most likely candidate, the study then applied several individual and multiple deletions to the five islands to observe the effects. These varied deletions only resulted in minor effects including physical abnormalities or a few missing digits. 
  When the experiment was taken a step further and applied a deletion of the entire 830 kilobase gene desert, the functionality of the entire Hox D locus was rendered inactive. This indicates that the neighboring gene desert, as an entire 830 kilobase unit (including the five island sequences within it), serves as an important regulator of a single gene that spans merely 50 kilobases. Therefore, these results hinted at the regulatory effects of flanking gene deserts. This study was supported by a later observation through a comparison between fluorescence in situ hybridization and chromosome conformation capture which discovered that the Hox D locus was the most decondensed portion in the region. This meant that it had relatively higher activity in comparison to the flanking gene deserts. Hence, the Hox D could be regulated by specific nearby enhancer sequences that were not expressed in unison. However, this does caution that proximity is inaccurate when either analytical method is used. Thus, associations between regulatory gene deserts and their target promoters seem to have variable distances and are not required to act as borders. 
  The variability in distance demonstrates that distance may be another important factor that is determined by gene deserts. For instance, distal enhancers may interact with their target promoters through looping interactions which must act over a certain distance. Thus, proximity is not an accurate predictor of enhancers: enhancers do not need to border their target sequence to regulate them. While this leads to a variation in distances, the average distance between transcription start sites and the interaction complex mediated by their enhancer elements is 120 kilobases upstream of the start site. Gene deserts may play a role in constructing this distance to allow maximal looping to occur. Given that the mechanism of enhancer complex formation is a fairly simply regulated mechanism (the structures that are recruited into the enhancing complex have various regulatory controls that control construction), more than 50% of promoters have several long-range interactions. Certain core genes even have up to 20 possible enhancing interactions. There is a curious bias for complexes to form only upstream of the promoters. Thus, given the correlation that many regulatory gene deserts appear upstream of their target promoters, it is possible that the more immediate role that gene deserts play is in long-range regulation of key sequences. 
  As the ideal formation of enhancer interactions requires specific constructs, a possible side-product of the regulatory roles of gene deserts may be the conservation of genes: to retain the specific lengths of loops and order of regulating genes hidden in gene deserts, certain portions of gene deserts are more highly conserved than others when passing through inheritance events. These conserved noncoding sequences (CNS) are directly associated with syntenic inheritance in all vertebrates. Thus, the presence of these CNSs could serve to conserve of large regions of genes. Although distance may vary in regulatory gene deserts, distance appears to have an upper limit in conservative gene deserts. CNSs were initially thought to occur close to their conserved genes: earlier estimates placed most CNSs in proximity of gene sequences. However, the expansion of genetic data has revealed that several CNSs reside up to 2.5 megabases from their target genes, with the majority of CNSs falling between 1 and 2 megabases. This range, which was measured for the human genome, is varied among different species. For instance, in comparison to humans, the Fugu fish has a smaller range, with an estimated maximum distance of a few hundred kilobases. Regardless of the difference in lengths, CNSs work in similar methods in both species. Thus, as functions differ between gene deserts, so do their contents.