To further our understanding of the regulation of vertebrate globin loci, we have isolated cosmids containing alpha- and beta-globin genes from the pufferfish Fugu rubripes. By DNA fluorescence in situ hybridization (FISH) analysis, we show that Fugu contains 2 distinct hemoglobin loci situated on separate chromosomes. One locus contains only alpha-globin genes (alpha-locus), whereas the other ...

Globin messenger RNA (mRNA) isolated from three patients homozygous for hemoglobin Lepore is shown to have a marked reduction of the amount of beta-like globin mRNA (Lepore-globin mRNA sequences) compared with alpha-globin mRNA by molecular hybridization. The relative amounts of alpha- and Lepore mRNA are similar to the amounts of alpha- and Lepore globin synthesized in intact cells and by isol...

To assess whether calcitonin is important in maintaining the integrity of bone the calcitonin gene of a young male patient with osteoporosis and no detectable plasma concentrations of calcitonin was studied. Genomic Southern blots with various restriction enzymes showed no large abnormalities in his calcitonin gene. Genomic clones representing his calcitonin gene were then analysed. His gene en...

Lemur beta-related globin genes have been isolated and sequenced. Orthology of prosimian and human epsilon-, gamma-, and beta-related globin genes was established by dot-matrix analysis. All of these lemur globin genes potentially encode functional beta-related globin polypeptides, though precisely when the gamma-globin gene is expressed remains unknown. The organization of the 18-kb brown lemu...

The ability to generate stable high-titer vectors that give rise to high levels of expression of transduced globin genes in erythroid cells is a prerequisite for effective retroviral-mediated globin gene therapy. The human beta-globin gene with its immediate flanking sequences does not contain all the regulatory elements necessary for regulated high-level and position-independent expression in ...

Transcription of the HIV-1 genome yields a single primary transcript, which is alternatively spliced to >30 mRNAs. Productive infection depends on inefficient and regulated splicing and appears to proceed in a tight 5' to 3' order. To analyse whether sequential splicing is mediated by the quality of splice sites or by the position of an intron, we inserted the efficient beta-globin intron (BGI)...

Comparison of the nucleotide sequences from the coding regions of the four mammalian beta-globin genes shows that different parts of these genes have evolved at two different rates. Those codons designating amino acids 1-20, 41-91 and 109-146 have accumulated substitutions in a random fashion as the molecular clock hypothesis would predict. The codons at positions 21-40 and 91 to 108 behave as ...

Generally, nonsense codons 50 bp or more upstream of the 3'-most intron of the human beta-globin gene reduce mRNA abundance. In contrast, dominantly inherited beta-thalassemia is frequently associated with nonsense mutations in the last exon. In this work, murine erythroleukemia (MEL) cells were stably transfected with human beta-globin genes mutated within each of the 3 exons, namely at codons...

Beta-globin gene families in eutherians (placental mammals) consist of a set of four or more developmentally regulated genes which are closely linked and, in general, arranged in the order 5'-embryonic/fetal genes-adult genes-3'. This cluster of genes is proposed to have arisen by tandem duplication of ancestral beta-globin genes, with the first duplication occurring 200 to 155 MYBP just prior ...

To investigate the function of transcription factor Sp1 in beta-like globin gene activation, we analyzed the recruitment of Sp1, fetal Krüppel-like factor 2 (FKLF2), and related factors at the human beta-globin locus in a human fetal liver and mouse erythroleukemia hybrid cell (A181gamma cell) that contains a single copy of human chromosome 11. Sp1 binds at the GT boxes of the cis-elements thro...