Long Range Regulation and Insulation of Domains.
Some genes respond to additional regulatory elements as well as to promoters and enhancers.
The existence of these elements was identified by the inability of a region of DNA including a gene and all known regulatory elements to be properly expressed when introduced into an animal as a transgene. The best characterized example is provided by the mouse beta-globin cluster. These genes are provided with a large number of regulatory elements, which have been analyzed in detail. In the case of the adult human beta-globin gene, regulatory sequences are located both 5' and 3' to the gene and include both positive and negative elements in the promoter region, and additional positive elements within and downstream of the gene. Some further regulatory sequence is required.