Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1852044 (HS3)
 171 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human beta locus control region (LCR) consists of five DNAse I hypersensitive sites (HS), four of which are erythroid specific and one, the further upstream located 5'HS5, is constitutive. To characterize the function of 5'HS5 we analyzed globin gene expression of various constructs containing HS3 as an enhancer, HS5, and the beta gene as a reporter. Expression was analyzed in stably transfected MEL cells. We found that the enhancing effect of hypersensitive site 3 is blocked when the HS5 is interposed between HS3 and the beta globin gene. These data suggest that the human 5'HS5 has the properties of a chromatin insulator.
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PMID:Hypersensitive site 5 of the human beta locus control region functions as a chromatin insulator. 806 37

Proper expression of the human beta-like globin genes is completely dependent on the presence of the locus control region or LCR, a region containing four DNase hypersensitive sites (HS1-4) situated 5' to the structural genes. Linkage of the LCR to a transgene results in copy number-dependent transcription, independent of the site of integration in the host genome. We have analysed a small region of the LCR (HS3) in transgenic animals to determine the minimal interactions that are required for this property. The results show that a specific combination of a G-rich sequence flanked on each side by one binding site for the transcription factor GATA1 is essential to obtain position-independent expression of a linked beta globin gene in erythroid cells. The overall transcriptional activity of HS3 is achieved through synergy with other combinations of similar binding sites.
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PMID:The minimal requirements for activity in transgenic mice of hypersensitive site 3 of the beta globin locus control region. 845 25

In this study we investigated the molecular bases of the beta-thalassemia intermedia phenotype in six patients belonging to two unrelated families of Sardinian descent. Sequence analysis of the beta globin gene from these patients detected, as the sole abnormality, the heterozygosity for the codon 39 nonsense mutation. The A gamma and Ggamma promoters as well as the HS2 and HS3 core sequences of the beta globin LCR from these patients, did not show any non-polymorphic nucleotide variation from the consensus sequence. One of the parents was heterozygous for codon 39 nonsense mutation but showed the beta-thalassemia carrier phenotype; the other was hematologically normal and had an entirely normal beta globin gene sequence. In both families, other members showed the typical hematological phenotype, clinically silent, of heterozygous beta thalassemia. To explain the thalassemia intermedia phenotype, we postulated the presence of an unknown molecular defect interacting with the beta globin gene mutation. Haplotype analysis excluded that this postulated defect lies in the beta globin gene cluster.
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PMID:Heterozygous beta-thalassemia with thalassemia intermedia phenotype. 942 15