Chromatin loops juxtapose distal enhancers with active promoters, but their molecular architecture and relationship with transcription remain unclear. In erythroid cells, the locus control region (LCR) and β-globin promoter form a chromatin loop that requires transcription factor GATA1 and the associated molecule Ldb1. We employed artificial zinc fingers (ZF) to tether Ldb1 to the β-globin prom...

Ten patients with thalassemia intermedia with variable severity and apparent simple heterozygosis for beta0 39 C>T nonsense mutation were submitted to clinical, hematologic and molecular studies. The presence of an unknown molecular defect (silent beta-thalassemia) unlinked to the beta cluster interacting with the heterozygous beta thalassemia, was previously postulated in these families. Analy...

AIMS Hypochromic microcytic anaemia is the hallmark phenotype of thalassaemia. Current phenotypical tests do not provide a diagnosis in a small proportion of patients with red blood cell microcytosis. We aim to evaluate the genetic basis of red cell microcytosis in these cases in our Chinese population. METHODS We identified from a large cohort of 1684 unselected requests for thalassaemia tes...

The human -globin locus has been extensively studied as a model of tissue and developmental stage-specific gene expression. Structural mapping of naturally occurring mutations, including transfection and transgenic studies, and the recent finding of intergenic transcripts have suggested that there are cis-acting sequence elements in the A – intergenic region involved in regulating and -globin g...

Gene therapy strategies requiring long-term high-level expression from integrated genes are currently limited by inconsistent levels of expression. This may be observed as variegated, silenced or position-dependent gene expression. Each of these phenomena involve suppressive chromatin structures. We hypothesized that by actively conferring an open chromatin structure on integrated vectors would...

Introduction: Beta-thalassemia is characterized by absence or reduced synthesis of the β-globin. Carriers of β-thalassemia, typically have microcytic hypochromic anemia and elevated hemoglobin HbA2 and normal HbF level. On the other hand carriers of severe alpha-thalassemia also have similar CBC parameters to that of β-thalassemia with normal HbA2 level. Co-presence of mutations in the β-globin...

In the present study we report the sequence haplotypes associated with 22 β-globin gene mutations present in Turkey. Nine nucleotide polymorphisms and an (AT)xTy motif located at the 5′ end of the β-globin gene form the sequence haplotypes that were investigated in 204 unrelated βthalassemia and wild-type chromosomes from Turkey. Twelve sequence haplotypes were observed in the chromosomes analy...

Background: Human β-like globin genes regulaon during development from embyonic to adult stage results in generaon of different types of hemoglobin with different funcons. As β-thalassemia and sickle cell disease are disorders of β-globin chain, epigenec drugs such as thalidomide and sodium butyrate which can induce γ-globin gene are considered as a novel therapeuc approach. Drugs effec...

Gene expression is primarily regulated by cis-regulatory DNA elements and trans-interacting proteins. Transcription factors bind in a DNA sequence-specific manner and recruit activities that modulate the association and activity of transcription complexes at specific genes. Often, transcription factors belong to families of related proteins that interact with similar DNA sequences. Furthermore,...

We report a new type of deletion of the fi globin gene cluster in the Italian population that confers a phenotype of hereditary persistence of fetal hemoglobin (HPFH) to the carriers. This deletion begins -5 kilobases (kb) 5’ to the #{246} globin gene and ends -30 kb 3’ to the fi globin gene. in close proximity to the 3’ end of an Indian HPFH. In all four previously described HPFH. a repetitive...