A single base substitution (A-G) at position -31 within the highly conserved proximal promoter element, the TATA box, was identified in the beta-globin gene cloned from a Japanese woman with beta +-thalassemia. It appears that she is homozygous for this specific allele, as determined by haplotype analysis using seven different polymorphic sites in the beta-globin gene cluster. Transient express...

Introduction: Beta-thalassemia is an autosomal recessive disease that occurs as a result of disorder in the (β-globin chains synthesis), and gold standard method for diagnosis genetic mutation analysis. It important to know distribution mutations according regions races. The aim this study document beta-globin gene beta-thalassemia major intermedia patients who were followed treated Sanliurfa p...

Nonsense mutations of the beta-globin gene are a common cause of beta-thalassemia. It is a hallmark of these mutations not only to cause a lack of protein synthesis but also a reduction of mRNA expression. Both the pathophysiologic significance and the underlying mechanisms for this surprising phenomenon have so far remained enigmatic. We report that the reduction of the fully spliced mutant be...

In human reticulocytes, the critical balancing of alpha- and beta-globin synthesis may be controlled in part by differential translation of the three major adult globin messenger RNAs (mRNAs), alpha 1, alpha 2, and beta. In this study, we determined, as a parameter of translational efficiency, the relative ribosome loading of these three mRNAs. Using oligonucleotide probes specific for the alph...

We have analyzed the chromatin structure of the human beta-globin locus in somatic cell hybrids resulting from the fusion of human non-erythroid cells and mouse erythroleukemia (MEL) cells. In these hybrids, the human adult beta-globin gene, but neither the embryonic nor fetal globin genes, is activated transcriptionally. In addition, the DNase I-resistant beta-like globin locus characteristic ...

Despite considerable concerns with pharmacological stimulation of fetal hemoglobin (Hb F) as a therapeutic option for the beta-globin disorders, the molecular basis of action of Hb F-inducing agents remains unclear. Here we show that an intracellular pathway including soluble guanylate cyclase (sGC) and cGMP-dependent protein kinase (PKG) plays a role in induced expression of the gamma-globin g...

The human beta-globin locus control region (LCR) consists of five erythroid-lineage-specific DNase I-hypersensitive sites (HSs) and is required for activation of the beta-globin locus chromatin domain and globin gene expression. Each DNase I-HS of the LCR consists of a highly conserved core element and flanking sequences. To analyze the functional role of the core elements of the HSs, we delete...

ANEMIA CAUSES A CHANGE IN THE TYPE OF CIRCULATING HEMOGLOBIN IN GOATS AND CERTAIN SHEEP: HbA (alpha(2)beta(2) (A)) is replaced by HbC (alpha(2)beta(2) (C)). We have isolated globin mRNA from erythroid cells of anemic and nonanemic animals to investigate the mechanism whereby anemia causes this switch. To study several stages in transition from beta(A) to beta(C) synthesis, active globin mRNA wa...

Processing of the beta major and beta minor globin pre-mRNAs has been compared in murine erythroleukemia cells induced to synthesize hemoglobin by dimethyl sulfoxide or hemin treatment, using both the Northern blot technique and S1 nuclease mapping with 3' and 5' end-labeled probes. The small intervening sequence of both beta-globin pre-mRNAs was removed in one step, although minor amounts of i...

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...