Communal Cell Death and P53 Mediated Transcriptional Control in Drosophila Melanogaster

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Title: Communal Cell Death and P53 Mediated Transcriptional Control in Drosophila Melanogaster
Author: Link, Nichole Lynn
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 .
URI: http : / /hdl .handle .net /2152 .5 /870
Date: 2011-08-26

Citation

Communal Cell Death and P53 Mediated Transcriptional Control in Drosophila Melanogaster. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /870 .

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