Conservation of position and sequence of a novel, widely expressed gene containing the major human alpha-globin regulatory element.

Abstract We have determined the cDNA and genomic structure of a gene (−14 gene) that lies adjacent to the human α-globin cluster. Although it is expressed in a wide range of cell lines and tissues, a previously described erythroid-specific regulatory element that controls expression of the α-globin genes lies within intron 5 of this gene. Analysis of the −14 gene promoter shows that it is GC rich and associated with a constitutively expressed DNase 1 hypersensitive site; unlike the α-globin promoter, it does not contain a TATA or CCAAT box. These and other differences in promoter structure may explain why the erythroid regulatory element interacts specifically with the α-globin promoters and not the −14 gene promoter, which lies between the α promoters and their regulatory element. Interspecies comparisons demonstrate that the sequence and location of the −14 gene adjacent to the α cluster have been maintained since the bird/mammal divergence, 270 million years ago.