in recent years of experience fetal hemoglobin (hbf) induction considers as novel therapeutic approach for β-thalassemia and sickle cell in therapeutic approaches. several pharmacologic agents such as hydroxyurea, azacytidine, butyrate deriviates and immunomodulator drugs like pomalidomide and lnalidomide could able to up-regulate hbf level with different molecular and epigenetic paterns (1-4)....

background: β-thalassemia considers worldwide public health disorders. novel fetal hemoglobin inducer agents such as thalidomide and sodium butyrate have been attended for ameliorating clinical complications of such disorders. material and methods: we used thalidomide and sodium butyrate for increasing the level of fetal hemoglobin in erythroid progenitors. briefly, after isolation of cd133+ st...

Objective(s): β-thalassemia is one of the most common genetic disorders in the world. As one of the promising treatment strategies, fetal hemoglobin (Hb F) can be induced. The present study was an attempt to reactivate the γ-globin gene by introducing a gene construct containing KLF1 binding sites to the K562 cell line. Materials and Methods: A plasmid containing a 192 bp sequence with two repe...

BACKGROUND Histone H3 lysine 4 (K4) methylation has been linked with transcriptional activity in mammalian cells. The WD40-repeat protein, WDR5, is an essential component of the MLL complex that induces histone H3 K4 methylation, but the role of WDR5 in human globin gene regulation has not yet been established. DESIGN AND METHODS To study the role of WDR5 in human globin gene regulation, we p...

objective(s): β-thalassemia is one of the most common genetic disorders in the world. as one of the promising treatment strategies, fetal hemoglobin (hb f) can be induced. the present study was an attempt to reactivate the γ-globin gene by introducing a gene construct containing klf1 binding sites to the k562 cell line. materials and methods: a plasmid containing a 192 bp sequence with two repe...

In human adult erythroid cells, lower than normal levels of Krüppel-like transcription factor 1 (KLF1) are generally associated with decreased adult β- and increased fetal γ-globin gene expression. KLF1 also regulates BCL11A, a known repressor of adult γ-globin expression. In seeming contrast to the findings in adult cells, lower amounts of KLF1 correlate with both reduced embryonic and reduced...

Thalassemia, an inherited quantitative globin disorder, consists of two types, α– and β–thalassemia. β–thalassemia is a heterogeneous disease that can be asymptomatic, mild, or even severe. Considerable research has focused on investigating its underlying etiology. These studies found DNA hypomethylation in the β–globin gene cluster significantly related to fetal hemoglobin (HbF) elevation. His...

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...

TAL1 is a key hematopoietic transcription factor that binds to regulatory regions of a large cohort of erythroid genes as part of a complex with GATA-1, LMO2 and Ldb1. The complex mediates long-range interaction between the β-globin locus control region (LCR) and active globin genes, and although TAL1 is one of the two DNA-binding complex members, its role is unclear. To explore the role of TAL...

Interferon (IFN)-γ is a proinflammatory cytokine that is linked to erythropoiesis inhibition and may contribute to anemia. However, the mechanism of IFN-γ-inhibited erythropoiesis is unknown. Activin A, a member of the transforming growth factor (TGF)-β superfamily, induces the erythropoiesis of hematopoietic progenitor cells. In this study, a luciferase reporter assay showed that IFN-γ suppres...