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Anti-silencing at Telomeres

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Title: Anti-silencing at Telomeres
Author: Chatterji, Arjun
Department: Department of Molecular and Cellular Biology
Program: Molecular and Cellular Biology
Advisor: Yankulov, Krassimir
Abstract: Gene silencing in Saccharomyces cerevisiae has been conclusively linked to histone deacetylation and the subsequent formation of heterochromatin. The participating histone deacetylases have also been well characterized. In contrast, the opposing histone acetyltransferases (HAT) and their mechanism of action remain elusive. In particular, very little is known about the effects of two of the nine HATs in S. cerevisiae, ESA1 and RTT109. The focus of my research was to test if these HATs influence the silencing of genes at the subtelomeric regions of S.cerevisiae and to assess their mechanism of action. To address these issues I used a panel of recombinant telomeric constructs that harbor the URA3 reporter gene. These constructs were inserted at the VIIL telomere of the mutant strains esa1-414 and ∆rtt109. The level of gene repression of the URA3 reporter in each construct in both of these strains has been assessed by a routine assay measuring the sensitivity of the strain to the drug 5-fluoro-orotic acid. My results indicate than none of these HATs plays a specific major role in gene repression at telomeres. Instead, they show general anti-silencing activity that cannot be linked to any specific sub-telomeric elements. Like many other HATs, Esa1 and Rtt109 seem to operate through global acetylation of histones rather than through specific recruitment. These results provide additional insight in the function of the HATs in gene silencing and suggest that there are multiple mechanisms that we do not yet understand. The information provided here would help in future studies to determine the mode of action of anti-silencers and subtelomeric elements involved in telomeric silencing. These issues are of fundamental significance and will contribute to the dynamic and expanding field of epigenetics.
URI: http://hdl.handle.net/10214/3738
Date: 2012-06
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