The erythroid Krüppel-like factor (EKLF) is a key regulatory protein in globin gene expression. This zinc finger transcription factor is required for expression of the adult beta globin gene, and it has been suggested that it plays an important role in the developmental switch from fetal gamma to adult beta globin gene expression. We have previously described a sequence element in the distal pr...

Previous studies have demonstrated that sickle cell disease (SCD) can be corrected in mouse models by transduction of hematopoietic stem cells with lentiviral vectors containing antisickling globin genes followed by transplantation of these cells into syngeneic recipients. Although self-inactivating (SIN) lentiviral vectors with or without insulator elements should provide a safe and effective ...

We have identified three unrelated individuals and three members of a family with the non-deletion form of Agamma-hereditary persistence of fetal hemoglobin (HPFH). Molecular analysis showed that each individual is a heterozygote for a previously described -195 Agamma (C-->G) mutation. The beta-globin gene cluster was studied using the polymerase chain reaction and related techniques. Haplotypi...

background: in the previous study, we have shown that the presence of a allele at position -588 in aγ-globin gene was highly frequent and closely associated with fetal hemoglobin elevation among β-thalassemia intermedia patients. therefore, we decided to investigate whether this allele (a allele at -588) could result in an increase in aγ-globin gene expression to ameliorate the severity of the ...

The expression of the beta-like globin genes is intricately regulated by a series of both general and tissue-restricted transcription factors. The hemapoietic lineage-specific transcription factor GATA-1 is important for erythroid differentiation and has been implicated in regulating the expression of the erythroid-specific genes including the genes of the beta-globin locus. In the human erythr...

To determine whether hemoglobin regulation is normal in diseases affecting beta-globin gene expression, globin synthesis was examined in members of a family of a patient with hereditary persistence of fetal hemoglobin/beta o-thalassemia (HPFH/beta o-thal). The HPFH defect is the Ghanian type II, with a deletion from psi beta 1 to at least 20 kb 3' to beta. The beta o-thal gene has the haplotype...

Recent studies indicate that a purified protein, activin A, belongs to the transforming growth factor beta (TGF-beta) superfamily. Similar to TGF-beta, activin A can have different biologic activities, depending on the target tissues. We used recombinant activin A to demonstrate a possible regulatory role of this protein in modulating human erythroid differentiation in the human erythroid cell ...

When a red cell nuclear extract (RCE) from adult chickens was injected into Xenopus oocytes along with the chicken beta globin gene, transcript levels were dramatically reduced compared to injection of DNA alone. The inhibitory action of the RCE was not specific to the beta globin gene since the Herpes thymidine kinase and Xenopus 5S RNA gene transcript levels were similarly reduced. Transcript...