The Ldb1/GATA-1/TAL1/LMO2 complex mediates long-range interaction between the β-globin locus control region (LCR) and gene in adult mouse erythroid cells, but whether this complex mediates chromatin interactions at other developmental stages or in human cells is unknown. We investigated NLI (Ldb1 homolog) complex occupancy and chromatin conformation of the β-globin locus in human erythroid cell...

Recently we cloned two globin gene clusters from the genome of medaka (Oryzias latipes): one designated the embryonic globin gene cluster (E1; (5')alpha0(3')-(3')beta1(5')-(5')alpha1(3')-(5')beta2(3')-(5')alpha2(3')-(3')alpha3(5')-(5')beta3(3')-(3')beta4(5')-(5')alpha4(3')-(3')psialpha(5')-(5')psibeta(3')) and the other the adult globin gene cluster (A1; (3')ad.alpha1(5')-(5')ad.beta1(3')-(3')a...

The Ldb1/GATA-1/TAL1/LMO2 complex mediates long-range interaction between the -globin locus control region (LCR) and gene in adult mouse erythroid cells, but whether this complex mediates chromatin interactions at other developmental stages or in human cells is unknown. We investigated NLI (Ldb1 homolog) complex occupancy and chromatin conformation of the -globin locus in human erythroid cells....

The mechanisms by which pharmacologic agents stimulate gamma-globin gene expression in beta-globin disorders has not been fully established at the molecular level. In studies described here, nucleated erythroblasts were isolated from patients with beta-globin disorders before and with butyrate therapy, and globin biosynthesis, mRNA, and protein-DNA interactions were examined. Expression of gamm...

Cell type-specific gene expression is regulated by chromatin structure and the transcription factors provided by the cells. In the present study, we introduced genes packaged into chromatin into target cells using a human artificial chromosome (HAC) and analyzed regulation of gene expression. The human beta-globin gene cluster was built into an HAC (globin-HAC) and introduced into mouse embryon...

β-thalassemia is the most common inherited disorder characterized by a reduction or absence of β-globin chain synthesis. So far, over 200 mutations have been identified that result in β-thalassemia. Most of the mutations are single nucleotide substitutions or deletions, or insertions in the β-globin gene or its flanking sequences. Heterozygous β-thalassemia usually presents with mild microcytic...

The DNaseI hypersensitive sites (HSs) of the human β-globin locus control region (LCR) may function as part of an LCR holocomplex within a larger active chromatin hub (ACH). Differential activation of the globin genes during development may be controlled in part by preferential interaction of each gene with specific individual HSs during globin gene switching, a change in conformation of the LC...

Objective: Our aim was to identify the beta globin gene cluster haplotypes for the beta thalassemia mutations in Turkey on a regional level. Beta thalassemia mutations included in this study were IVS-I-110 (G>A), FSC 8/9 (+G), IVS-II-1 (G>A), IVS-I-5 (G>C), IVS-I-1 (G>A), IVS-I-6 (T>C), and FSC 8 (-AA). Methods: We studied 22 unrelated patients with β-thalassemia major and 72 unrelated healthy ...

High-level beta-globin gene expression is dependent on the presence of the locus control region (LCR), a powerful regulatory element physically characterized by five DNase I-hypersensitive sites (HS), designated HS1-HS5. Of these, HS3 contains seven GT motifs that are essential for its activity. One of the motifs, GT6, has been shown by in vivo footprinting to display the largest difference in ...

Lepore globin is synthesized in markedly diminished amounts (approximately 10% to 15% of normal beta-globin) in human erythroid cells. To study the molecular mechanisms responsible for the diminished biosynthesis of Lepore globin, the Lepore-Boston gene was cloned from a charon phage DNA library and expressed in HeLa cells. Northern blotting and S1 nuclease analyses indicated that the Lepore ge...