2002-11-20
Activation, Regulation and Transcription of the Human and Murine Globin Loci.
Publication
Publication
Activatie, regulatie en transcriptie van de humane en muizen globine loci
Hemoglobin is the carrier of oxygen in the bloodstream. It is a tetrameric protein composed of two α-globin chains and two β-globin chains. These chains are encoded by the α- and β-globin gene loci. The globin loci are located on separate chromosomes and are composed of several developmentally regulated genes and regulatory elements located both upstream of the gene loci and around the individual genes. Lesions in the globin clusters give rise to blood disorders known as hemoglobinopathies. The study of the molecular basis of these disorders led to the identification of many regulatory elements of the globin loci, including the locus control region (LCR). The β-globin locus is one of the best-studied multi gene loci and has been extensively used as a model system for the study of gene regulation. The aims of this thesis are to study the mechanism of transcriptional activation of the globin loci, the role of the hypersensitive sites in LCR function and the further characterisation of putative γ-globin regulatory elements. In conclusion, the studies presented here show: 1. that there is evidence for a stochastic basis for activation of globin gene expression; 2. that the LCR does function as a holocomplex, but also that the individual hypersensitive sites act differently on each globin gene; 3. that the regulation of the individual globin genes is very complex and probably involves the interaction of various combinations of elements during different stages of development.
Additional Metadata | |
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, , , | |
Grosveld, Prof. Dr. F.G. (promotor) | |
F.G. Grosveld (Frank) | |
hdl.handle.net/1765/1146 | |
Organisation | Erasmus MC: University Medical Center Rotterdam |
de Krom, M. (2002, November 20). Activation, Regulation and Transcription of the Human and Murine Globin Loci.. Retrieved from http://hdl.handle.net/1765/1146 |
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Krom Dissertation.pdf Final Version , 1mb | |
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Krom_front.gif , 21kb |