Conservation of position and sequence of a novel, widely expressed gene containing the major human alpha-globin regulatory element.
We have determined the cDNA and genomic structure of a gene (-14 gene) that lies adjacent to the human alpha-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 alpha-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 alpha-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 alpha-globin promoters and not the -14 gene promoter, which lies between the alpha promoters and their regulatory element. Interspecies comparisons demonstrate that the sequence and location of the -14 gene adjacent to the alpha cluster have been maintained since the bird/mammal divergence, 270 million years ago.
Vyas
P
P
MRC Molecular Hematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
Vickers
M A
MA
Picketts
D J
DJ
Higgs
D R
DR
D000595:Amino Acid Sequence; D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D005075:Biological Evolution; D001717:Birds; D002460:Cell Line; D002645:Chickens; D017124:Conserved Sequence; D017931:DNA Primers; D018076:DNA, Complementary; D005091:Exons; D005786:Gene Expression Regulation; D005914:Globins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007438:Introns; D008322:Mammals; D008969:Molecular Sequence Data; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D016385:TATA Box; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D018076:DNA, Complementary; D011994:Recombinant Proteins; D005914:Globins