Communal Cell Death and P53 Mediated Transcriptional Control in Drosophila Melanogaster

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Communal Cell Death and P53 Mediated Transcriptional Control in Drosophila Melanogaster

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dc.contributor.advisor Abrams, John en
dc.creator Link, Nichole Lynn en
dc.date.accessioned 2011-08-26T17:33:49Z en
dc.date.available 2011-08-26T17:33:49Z en
dc.date.issued 2011-08-26T17:33:49Z en
dc.identifier.other 758979165 en
dc.identifier.uri http://hdl.handle.net/2152.5/870 en
dc.description.abstract Apoptosis is essential for all metazoan development. The key component that functions in apoptosis, the apoptosome, is a molecular machine that initiates caspase activation and is conserved throughout the animal kingdom. Drosophila strains that are mutated for genes encoding the apoptosome show pronounced defects in programmed cell death (PCD). Using a characteristic phenotype associated with mosaic animals, we conducted a screen in Drosophila to discover new regulators or effectors of the apoptosome. Using this model, we also discovered a unique communal form of cell death where large regions of epithelial cells are eliminated within minutes. We also produced 'saturation tile' arrays by digital optical chemistry for an unbiased sampling of transcriptional activity in the Drosophila genome. We found that the scope of unannotated transcriptional activity is extensive and widespread. A dominant population of noncanonical transcripts was stress-responsive and required p53, a master regulator of conventional stress-responsive target genes in vertebrates and invertebrates. This prompted us to examine stimulus dependent activity surrounding a single p53 enhancer in our tiled region. Through genetic analyses, we showed that this enhancer coordinates stimulus dependent induction of multiple genes spanning over 300kb throughout the Reaper region. Surprisingly, this same enhancer regulated a gene positioned across the centromere at distances over 20Mb and also controlled at least one gene mapping to a different chromosome. Chromosome conformation capture analyses placed this enhancer in close proximity to these distant targets in vivo through specific DNA looping and these interactions were influenced by p53. Therefore, a single p53 enhancer is necessary and sufficient for long range, multigenic regulation in cis and in trans. en
dc.language.iso en en
dc.subject Apoptosis en
dc.subject Drosophila Proteins en
dc.subject Gene Silencing en
dc.title Communal Cell Death and P53 Mediated Transcriptional Control in Drosophila Melanogaster en
dc.type Thesis en
thesis.degree.grantor Graduate School of Biomedical Sciences en
thesis.degree.name Doctor of Philosophy en
thesis.degree.level Ph.D. en

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