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.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:BVAU.2429/320 |
| Date | 05 1900 |
| Creators | Doheny, James |
| Publisher | University of British Columbia |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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