Description
- Abstract:
- In budding yeast, mating-type identity is determined genetically by the MAT locus, which encodes a set of transcriptional regulators that direct the cell to execute a specific genetic program. Even though mating type is genetically encoded, yeast cells are able to switch their phenotype by replacing the allele present at MAT with an allele encoding a different set of regulators. After a switch, the regulators that were expressed in the previous type must be inactivated for the cell to properly establish its new phenotype. To accomplish this, each of the mating-type regulators is constitutively targeted for rapid degradation in the proteasome. However, for the a2 repressor, rapid destruction would seem to be incompatible with its function. a2 represses a-cell specific genes (asg) by recruiting the Tup1/Ssn6 co-repressor complex, and in spite of its instability, repression engendered by a2 is both stable and robust. I have investigated the functionally engaged pool of a2 and found that interaction with Ssn6 altered the dynamics of a2-target gene interactions, allowing it to remain bound to its targets while the unbound pool was degraded. This effect depended on Isw2, suggesting that a repressive chromatin structure may shield the DNA-bound pool from destruction, and allow the formation of a stable co-repressor complex. In spite of its apparent stabilization, I found that once a2 dissociated from its targets, a-specific gene expression was activated extremely rapidly. Activation kinetics could not be explained by the pre-loading of RNA polymerase II or TBP. Unexpectedly, I found that each of the asg were acetylated on lysine 9 of histone H3 while they were in the repressed state. Both histone acetylation and asg activation kinetics were dependent on Gcn5, suggesting that the acetylation of repressed asg primes them for rapid activation. Furthermore, both the acetylation of repressed asg, and the binding of Gcn5 to asg, depended on the Tup1/Ssn6 complex, suggesting that the co-repressor complex directs the priming of asg. Similar results were observed for the rapidly induced GRE2 gene. I conclude that co-repressor directed acetylation of histones might be a commonly used mechanism to enable the rapid activation of repressed genes.
- Notes:
- Thesis (Ph.D.) -- Brown University (2010)
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Citation
DeSimone, Alec M.,
"The Dynamic Interactions of the alpha2 Repressor Engender Robust Repression of Developmentally Regulated Genes while Priming them for Rapid Activation"
(2009).
Biology and Medicine Theses and Dissertations, Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z0ZG6QJQ
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