Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new deletion of the beta-globin gene cluster has been characterized in two Italian brothers who are heterozygous carriers of a G gamma A gamma hereditary persistence of fetal hemoglobin (HPFH). Restriction endonuclease mapping and DNA sequencing of the region encompassing the breakpoint show that the deletion starts 3.2 kilobases (kb) upstream from the delta gene and ends within the enhancer region 3' to the beta-globin gene. Here the deletion removes one of the four binding sites for an erythroid specific transcriptional factor (NF-E1). The molecular comparison of the new deletion with others of similar size and location but associated with a delta beta-thalassemia phenotype suggests that the residual enhancer element, relocated near gamma genes, may increase the fetal hemoglobin (HbF) expression above the level observed in delta beta-thalassemia.
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PMID:A new hereditary persistence of fetal hemoglobin deletion has the breakpoint within the 3' beta-globin gene enhancer. 168 88

Using in vitro assays, we show that nuclear proteins related to the Sp1 and GT-1 factors bind to a CACCC box sequence in the human beta-globin enhancer, adjacent to binding sites for the erythroid-specific factor NFE1 and the ubiquitous factor CP1. The same proteins are known to bind to the proximal, but not to the distal, CACCC, box in the human beta-globin promoter. A C G mutation in the promoter CACCC box, known to cause beta-thalassemia, greatly decreases protein binding to the CACCC box; the same effect is obtained when this mutation is introduced into the enhancer CACCC box.
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PMID:The same nuclear proteins bind the proximal CACCC box of the human beta-globin promoter and a similar sequence in the enhancer. 280 90