Abstract
The strongest evidence for the existence of an important control in the flanking region of the globin gene domain was provided by the analysis of human γβ-thalassaemias.1,2 Patients with heterozygous Dutch γβ-thalassaemia have a deletion that removes 100 kb of DNA, leaving the β-globin gene and the promoter and enhancer regions intact. However, it abolishes expression of the deleted chromosome and leaves the gene in an inactive chromatin configuration.3–5 The wild-type allele on the other chromosome is expressed at normal levels, indicating that there is no shortage of trans-acting factors. This suggests a cis effect on β-globin gene transcription, which could be caused by a loss of positive acting elements or by the juxtaposition of the intact β-globin gene and sequences that remain in an inactive chromatin configuration in erythroid cells. The first indication that positive acting sites may be involved in activation of the β-globin domain came with the observation of erythroid specific DNasel hypersensitive sites that map 6–18 kb upstream from the ε-globin gene (Fig. 1).6–8
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Grosveld, F. et al. (1990). The β-Globin Dominant Control Region. In: Harris, T.J.R. (eds) Protein Production by Biotechnology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1565-0_10
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DOI: https://doi.org/10.1007/978-1-4613-1565-0_10
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