Gene duplication is thought to play an important role in the co-option of existing protein functions to new physiological pathways. The globin superfamily of genes provides an excellent example of the kind of physiological versatility that can be attained through the functional and regulatory divergence of duplicated genes that encode different subunit polypeptides of the tetrameric hemoglobin ...

In mammals, the complex tissue- and developmental-specific expression of genes within the β-globin cluster is known to be subject to control by the gene promoters, by a locus control region (LCR) located upstream of the cluster, and by sequence elements located across the intergenic regions. Despite extensive investigation, however, the complement of sequences that is required for normal regula...

Methylation of cytosines in the dinucleotide CpG has been shown to suppress transcription of a number of tissue-specific genes, yet the precise mechanism is not fully understood. The vertebrate globin genes were among the first examples in which an inverse correlation was shown between CpG methylation and transcription. We studied the methylation pattern of the 235-bp rho-globin gene promoter i...

Transgenic mice were generated which carried the adult alpha and beta-globin genes and the major tadpole specific beta-globin gene of Xenopus laevis. The adult specific alpha and beta genes were found to express in erythroid tissues in adult mice, while the major tadpole specific beta gene (beta T1) was expressed in blood from 12.5 day embryos. The pattern of expression of the beta T1 gene duri...

To study the expression of globin genes in human cells, human epsilon-globin genes were transferred into a K562 cell line, Bos, which synthesizes very low amounts of epsilon-globin mRNA. A plasmid (pSV2neo-epsilon) containing a complete epsilon-globin gene and 2 kilobases (kb) of 5' flanking DNA as well as a neomycin-resistance gene and a simian virus 40 origin of replication was transfected in...

T HE HUMAN a-globin gene complex on chromosome 16 consists of two adult a-genes (al and ct2), an embryonic c-gene, and associated pseudogenes.’ Disorders of a-chain synthesis result in diminished (a thalassemia) or absent (a#{176}thalassemia) a-chain production from the affected chromosome. Molecular analysis has revealed ddetion and nondeletion defects of which, unlike the fl-thalassemias, del...

Activation of chicken globin gene transcription has been demonstrated in chicken erythrocyte--rat L6 myoblast heterokaryons. The globin mRNA is polyadenylylated and is translated into adult chicken alpha A-, alpha D-, and beta-globin polypeptides. No fetal globin mRNA or globin polypeptides were detected. Heterokaryons between chicken erythrocytes and mouse neuroblastoma cells or hamster BHK ce...

The delineation of the thalassemia syndromes started in the late 1950s with the distinction of alpha and beta thalassemias and the initial studies that pointed out to the considerable genetic heterogeneity of these disorders. Molecular investigations, however, had to wait for the development of recombinant DNA and molecular cloning techniques in the 1970s. The thalassemias were the first human ...

HE HUMAN p-GLOBIN locus contains five funcT tional genes arranged 5' E-Gy-Ay-6-P 3' in the order of their expression during development.' Six to 18 kb upstream of the eglobin gene are a series of four DNase I hypersensitive sites that are erythroid specific and developmentally stable, ie, present regardless of which specific globin genes are active.'z3 Reverse genetics experiments have shown th...