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The recently identified theta-globin gene subfamily consists of the theta 1-globin gene located downstream from the alpha 1-globin gene, and several other members including at least one truncated, processed pseudogene psi theta 2 (refs 1,6). Unlike the theta 1-globin genes of the rabbit and galago, the structure of these genes in the orangutan and baboon and their flanking regions show no apparent defects that would prevent their expression. Both theta 1-globin genes are split into three exons with the potential to code for a polypeptide of length 141 amino acids. Besides differing by 26% in replacement-site substitutions, the theta 1 and alpha 1-globin genes of the orangutan and baboon also differ in their promoter structures, in the use of TGA versus TAA as the termination codon, and in the use of AGTAAA versus AATAAA as the polyadenylation signal. In contrast, the two theta 1-globin genes from primates only differ by 1.7% in the replacement-site substitutions. Here we present the complete DNA sequence of a cloned theta 1-globin gene of humans, and show that it contains no apparent defects that would abolish its expression. Furthermore, by primer extension of single-stranded oligonucleotide probes, we show that the theta 1-globin gene of humans is transcribed in an erythroleukemia cell line K562. Three messenger RNA species were detected, with 5'-ends mapping to approximately 70 base pairs (bp) downstream from a TATA promoter sequence, at 8 bp downstream from a GGGCGG promoter sequence and at 40 bp upstream from the ATG inititrion codon, respectively. Haemin treatment of the K562 cells slightly enhances the level of the longest theta 1-transcript. Our results provide strong evidence that the theta 1-globin gene of humans is transcriptionally active in cells of erythroid origin, and suggests the presence of a functional theta 1-polypeptide in specific cells, possibly those of early erythroid tissue.

Type

Journal article

Journal

Nature

Publication Date

1988

Volume

331

Pages

94 - 96

Keywords

Amino Acid Sequence Base Sequence Gene Expression Regulation Genes, Structural Globins/biosynthesis/*genetics Human Leukemia, Erythroblastic, Acute Molecular Sequence Data Recombinant Proteins/biosynthesis Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Tumor Cells, Cultured