The experimental work presented in this thesis pertains to the regulation of gene expression and focuses on the regulation of the B globin genes. The expression of the globin genes is restricted to the erythropoietic tissue and is regulated during development. Therefore the study of globin gene expression can yield valuable insights in how organisms regulate their genes in a coordinated tissue and developmental manner. Two main issues will be addressed in the chapters of this thesis. The first concerns the mechanism by which a transcriptionally competent domain is formed in the chromosomal environment. This topic is the subject of Chapter 2. Once transcriptionally competent domains are formed, gene transcription can take place and it is orchestrated by factors that interact specifically with the regulatory elements of the gene itself. This interaction determines tissue specificity and developmental regulation of a gene. The second issue addressed concerns the transcriptional regulation of the ~ globin gene via their CCAAT boxes studied through NFE6, a factor that binds to these elements (Chapters 3 and 4). NF-E6 interaction with its target sequence participates in the change in globin gene expression concomitant with the progressive changes that occur during the development of an embryo to a fetus.

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F.G. Grosveld (Frank)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam