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...

BACKGROUND beta-thalassemia is one of the most common genetic diseases in the world and requires extensive therapy. Lentiviral-mediated gene therapy has been successfully exploited in the treatment of beta-thalassemia and showed promise in clinical application. Using a human beta-globin transgenic mouse line in a beta-thalassemia diseased model generated with a lentiviral-mediated approach, we ...

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...

During development, human beta-globin locus regulation undergoes two critical switches, the embryonic-to-fetal and fetal-to-adult hemoglobin switches. To define the role of the fetal (A)gamma-globin promoter in switching, human beta-globin-YAC transgenic mice were produced with the (A)gamma-globin promoter replaced by the erythroid porphobilinogen deaminase (PBGD) promoter (PBGD(A)gamma-YAC). A...

Background Follicle stimulating hormone (FSH)- a hetrodimeric glycoprotein- is secreted by pituitary gland. This hormone stimulates growth and maturation of the follicles in females and sperms in male. Up to now, glycoprotein hormones such as FSH have produced in different cell lines. Among of the mammalian expression systems, the Chinese hamster ovary cells (CHO) have taken into consideration ...

introduction: beta thalassemias are a heterogenous group of autosomal recessive disorders, characterized by reduced or absent production of the b-globin chain by the affected allele. transplantation of allogenic hematopoietic stem cells (hsc) is a curative approach but this therapeutic option is not available to the majority of patients. transplantation of genetically corrected autologous hsc i...

OBJECTIVE Four combinations of five neutral sequence changes at rs713040, rs10768683, rs7480526, rs7946748, and rs1609812 occurring in the human beta globin gene defined as frameworks have been reported in beta globin gene. Here we report for the frequency of these frameworks in thalassemia major patients of North Iran. METHODS Beta globin gene frameworks of 46 thalassemia major patients of N...

Regulated expression of genes in the beta-globin cluster depends upon sequences located between 5 and 20 kb upstream of the epsilon gene, known as the locus control region (LCR). beta-Globin expression in murine erythroleukemia (MEL) cells depends on NF-E2, a transcription factor which binds to enhancer sequences in the LCR. To gain insight into the mechanism of globin gene activation by NF-E2,...

Interruption of the normal fetal-to-adult transition of hemoglobin expression should largely ameliorate sickle cell and beta-thalassemia syndromes. Achievement of this clinical goal requires a robust understanding of gamma-globin gene and protein silencing during human development. For this purpose, age-related changes in globin phenotypes of circulating human erythroid cells were examined from...

To further our understanding of the regulation of vertebrate globin loci, we have isolated cosmids containing alpha- and beta-globin genes from the pufferfish Fugu rubripes. By DNA fluorescence in situ hybridization (FISH) analysis, we show that Fugu contains 2 distinct hemoglobin loci situated on separate chromosomes. One locus contains only alpha-globin genes (alpha-locus), whereas the other ...