Regulation of 5' HoxD genes through interactions with two upstream enhancers. Two enhancers, GCR and Prox, are situated upstream of the HoxD genes, separated from each other by a gene called 'Luna Park' (Lnp). Both enhancers attach together to a region between HoxD-13 and the next upstream gene, Evx2, and from there interact with the genes in the HoxD cluster. The intensity of expression is then determined by two factors. First is the proximity of a gene to the enhancers, such that HoxD-13 is expressed at a much higher level than HoxD-10. Second, the differential affinity of the promoters of the HoxD genes for the enhancer complex also modulates their expression (not shown here). Reproduced with permission from .