The identification of drugs capable of reactivating γ-globin to ameliorate β-thalassemia and Sickle Cell anemia is still a challenge, as available γ-globin inducers still have limited clinical indications. High-throughput screenings (HTS) aimed to identify new potentially therapeutic drugs require suitable first-step-screening methods combining the possibility to detect variation in the γ/β glo...

background: we aimed to determine the incidence of co-inheritance as well as interaction of sickle cell trait (sct) and α thal /β thal mutations in south and south central of iran. method: we employed a pcr and restriction fragment length polymorphism techniques to confirm diagnosis of sickle cell trait. all subjects were screened for any α/β -thalassemia mutations using a gap-polymerase chain ...

Lemur P-related globin genes have been isolated and sequenced. Orthology of pro-simian and human E-, y-, and P-related globin genes was established by dot-matrix analysis. All of these lemur globin genes potentially encode functional P-related globin polypeptides, though precisely when the y-globin gene is expressed remains unknown. The organization of the 18-kb brown lemur P-globin gene cluste...

Human embryonic zeta and epsilon globin chains are synthesized in yolk sac-derived primitive erythroid cells, and decrease rapidly during definitive erythropoiesis. Examination of zeta and epsilon globin expression at the cellular level using dual-color immunofluorescence staining with specific monoclonal antibodies showed that embryonic globin proteins are present in definitive erythroid cells...

Details are presented of the in vitro synthesis of double-stranded DNA complementary to purified Xenopus globin messenger RNA, using a combination of reverse transcriptase, fragment 'A' of E. coli DNA polymerase 1 and S1 endonuclease. After selection of duplex DNA molecules approaching the length of Xenopus globin messenger RNA by sedimentation of the DNA through neutral sucrose gradients, the ...

This report describes observations on the rate of heme and globin synthesis within the maturation period of human marrow erythroid cells. Such studies have been designed to examine the hypothesis that heme and globin are synthesized with temporal independence during erythroid cell maturation and to establish the normal relationship of heme and globin synthesis. With such data it is hoped that f...

The a b i l i to generate stable high-titer vectors that give rise to high levels of expression of transduced globin genes in erythroid dls is a prerequisite for dfective retrovird-diated globin gene therapy. The human #%globin gene with its immediate flanking sequences does not contain all the regulatory elements necessary for regulated high-level and position-independent expression in erythro...

The developmental switch from human fetal (gamma) to adult (beta) hemoglobin represents a clinically important example of developmental gene regulation. The transcription factor BCL11A is a central mediator of gamma-globin silencing and hemoglobin switching. Here we determine chromatin occupancy of BCL11A at the human beta-globin locus and other genomic regions in vivo by high-resolution chroma...

Increased fetal hemoglobin (HbF) in b-globin gene disorders ameliorates the clinical symptoms of the underlying disease. 5-azacytidine, butyrate and hydroxyurea, have been shown to activate g-globin gene expression. It has also been found that hematopoietic growth factors can influence expression of g-globin in erythroid cultures and in animal models. This study was designed to evaluate the in ...

Changes in gamma-globin gene methylation accompany the fetal to adult globin switch in man. Using somatic cell hybrids made by fusing mouse erythroleukemia and human fetal erythroid cells, we asked whether methylation is a cause or a consequence of gamma-gene inactivation during development. These hybrids initially express human gamma-globin but switch with time in culture to adult globin gene ...