Transcriptional regulation of the B-Globin locus: of mice and men
(Regulatie van transcriptie van de B-globine loci: in muizen en in mensen)
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The aim of this thesis was to get more insight into the mechanism of transcriptional activation of the human B-globin locus. Chapter 1 serves as an introduction to chromatin. The different aspects of chromatin are briefly described. Chapter 2 reviews the work on the human B-globin locus over the last decade. This review aims to present some background information for the more. recent experiments that are described in chapters 3 to 6. Chapter 3 shows the results of individual hypersensitive site deletions of the p-globin LCR: the trans genes become subject to position effects and a novel position effect is described. In chapter 4 one of the parameters that is important in the activation of the globin genes is described: the frequency of LCR-gene . interactions. Chapter 5 presents evidence that the locus control region activates only one gene at a time. Finally in chapter 6 detailed analyses of the mouse p-globin locus is shown and the data suggest that the mechanism of gene activation is conserved during evolution. In concluding remarks I discuss some implications of our work and future experiments. For more detailed considerations of specific findings, the reader is referred to the discussion of chapters 3 to 6.
Stichting voor Nederlands Wetenschappelijk Onderzoek (NWO)