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Title: Investigating a role for E2A in the regulation of gene conversion and somatic hypermutation
Author: Conlon, T. M.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2006
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To investigate a potential role for E2A in gene diversification post rearrangement the chicken DT40 B cell line has been chosen as a model. This cell line is genetically tractable and can undergo both gene conversion and SHM. Here I describe cloning of the chicken orthologue of the human transcription factor E2A. Alternative splicing can give rise to either E47 or E12 proteins, which function as transcription factors in transient assays. Their activity depends on the presence of transcriptional activation domain I. They can also be inhibited by the dominant negative proteins Id1 and Id3. Overexpressing Id1 and Id3 in DT40 cells significantly reduced the level of IgV gene conversion occurring. This was accompanied by a decrease in the level of IgL gene transcription. We therefore have evidence from the endogenous Ig locus that gene conversion like SHM correlates with the level of transcription. Conversely, overexpressing E47 in DT40 cells leads to a dramatic increase in gene conversion rates. Interestingly this does not correlate with either IgL or AID transcription levels which remain unchanged. Thus, E47 is the first transcription factor identified as an activator of gene conversion whose function does not depend on increasing the rate of transcription of either the AID or IgL genes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available