UBC Theses and Dissertations
A study of the composition and function of telomeric chromatin in drosophila melanogaster. Doheny, James
The telomeres of most organisms are characterized by a protein-capping complex that protects chromosome ends, a series of repetitive subtelomeric sequences known as Telomere-Associated Sequences (TAS), and a behavioral phenomenon known as Telomere Position Effect (TPE). TPE is a phenomenon whereby normally active genes become repressed and silenced if relocated near to telomeres, and is thought to be a property of the proteins that constitute telomeric heterochromatin. Genetic dissection was used to exploit this phenomenon in order to identify components of telomeric heterochromatin in Drosophila melanogaster. Using genetic dissection, followed by a chromatin analysis technique known as Chromatin ImmunoPrecipitation (ChIP) I was able to identify three proteins, HDAC1, SU(VAR)3-9, and HP1c, as integral components of telomeric heterochromatin in Drosophila. HDAC1 and SU(VAR)3-9 are both believed to be involved in the gene-silencing process, and thus, their presence at telomeres could explain the phenomenon of TPE. Furthermore, I found that these proteins were specifically associated with the TAS region on the centromere-proximal side of the HeTA transposable elements that maintain telomere length in Drosophila. As a result of this, I proposed a model, which I call the ‘pairing-sliding model of telomere length control in Drosophila,’ which proposes that temporary incorrect pairing of Drosophila telomeres results in the deacetylation and subsequent methylation of the nucleosomes associated with the HeT-A and TART elements by TAS-associated HDAC1 and SU(VAR)3-9, resulting in these elements being transcriptionally silent. Thus, I propose that the TAS region, and the HDAC1 and SU(VAR)3-9 associated with it play a role in the negative regulation of telomere length in Drosophila.
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