Title page for ETD etd-06262008-142201

Type of Document Dissertation
Author Jambunathan, Nithya
URN etd-06262008-142201
Title Genetic and Mechanistic Analysis of Heterochromatin Spreading in the Yeast S.cerevisiae
Degree Doctor of Philosophy (Ph.D.)
Department Biochemistry (Biological Sciences)
Advisory Committee
Advisor Name Title
Donze, David Committee Chair
DiMario, Patrick J. Committee Member
Hart , Craig M. Committee Member
Larkin, John C. Committee Member
Franke, Donald E. Dean's Representative
  • transposon
  • SIR3
  • MAT
  • eukaryote
  • Saccharomyces
  • remodelling
  • nucleosome
Date of Defense 2008-04-09
Availability unrestricted
RNA Polymerase III transcribed tRNA genes are implicated in a wide variety of chromosome organizational functions that includes the ability to act as a boundary to heterochromatic silencing. A tRNA gene has been shown to be a major component of the barrier that prevents spreading of silencing from the HMR locus to the downstream GIT1 gene on chromosome III in S.cerevisiae. Our results suggest that additional proteins are involved in maintaining the boundary function of this tRNA gene. Mutations or deletions of the genes coding for these additional proteins have been shown to either weaken the boundary or enhance silencing. This mutational analysis identified YTA7, a novel bromodomain containing gene, as being required for full barrier activity of the HMR tRNA gene. This provided some of the first evidence demonstrating a role for bromodomain proteins in boundary function. RPD3, a histone deacetylase gene was also identified by our mutational analysis, as when deleted caused an increase in the spread of silencing downstream of the boundary tRNA gene. Our results suggest that this spreading of heterochromatic silencing occurs in spite of this tRNA gene remaining transcriptionally active. This suggests that heterochromatic silencing can bypass active regions along a chromosome to silence downstream genes.
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