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Title: Regulation of the mouse immunoglobulin heavy chain locus by 3’ regulatory elements
Author: Bunting, S. F.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2006
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The expression of mammalian genes requires recruitment of RNA polymerase to the genic promoter. This process is regulated by enhancer elements, which have been hypothesised to act by making physical contacts with the gene mediated by chromosome loops. In the case of the recombined immunoglobulin heavy chain (IgH) gene, expression is regulated by an intronic enhancer located between the variable and constant region exons. In vivo and in vitro studies indicate that an additional, distal regulatory region at the 3’ end of the Immunoglobulin Heavy Chain locus has enhancer activity in B cells. This 3’ regulatory region (3’RR) may also regulate class switch recombination and act as a Locus Control Region (LCR). I have used the recently developed Capturing Chromosome Conformation assay to investigate the hypothesis that the 3’RR and IgH gene interact directly. I have shown for the first time that such a direct, physical interaction does occur when the 3’RR is active. I have used this approach in resting and n vitro activated splenic B cells to infer the relative contributions of the four HSs to enhanced transcription. My results also demonstrate that the 3’RR is involved in class switch recombination. My work has further focuses on investigating mechanisms that might facilitate the IgH gene-3’RR interaction. A key candidate is intergenic transcription, which has previously been associated with LCR activity in several other mammalian loci. My studies have shown that intergenic transcription occurs at distinct sites in the 3’ regulatory region at sequential stages of B cell differentiation. This transcription may have a role in organising chromatin loops to facilitate the interactions seen between the 3’RR and the IgH gene.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available