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UBC Theses and Dissertations

Coordinated activities of chromatin modifying complexes in DNA regulation in Saccharomyces cerevisiae Lu, Ya Ting Phoebe


As the sole carrier of genetic information, DNA does not exist as a naked template in the eukaryotic genome; instead DNA exists as a nucleoprotein complex. Wrapped around specialized histone proteins, DNA and histones are assembled into the organized chromatin structure. The chromatin structure is regulated by a wide assortment of factors to facilitate access to the genetic material while at the same time compacting the genome. Perhaps it is not surprising that the coordinated activities of multiple chromatin-modifying complexes are necessary to regulate the many biological process occurring on DNA. We are beginning to understand how chromatin-modifying mechanisms cooperate to regulate gene promoters and define unique chromatin neighbourhoods. In this dissertation, I explore the functional connections between chromatin remodeling complexes, histone chaperones and histone variants in various aspects of chromatin biology. Focusing on the synthetic genetic interaction between ASF1 and YAF9, I uncovered the cooperative activities of histone chaperone and the SWR1-C H2A.Z exchange complex in maintaining heterochromatin boundaries. Furthermore, I also identified that H2A.Z occupancy at gene promoters is partially dependent on Asf1-mediated H3K56 acetylation. I specifically studied the functional relationship between H3K56 acetylation and H2A.Z occupancy. I determined that acetylation of H3K56 was required for maintaining H2A.Z levels at gene promoters. Furthermore, I discovered that H3K56 acetylation was also important in positioning H2A.Z containing nucleosomes at promoters. Lastly, I explored the specific features required for NuA4 structure and histone acetylation function. I uncovered a novel regulatory relationship between the Eaf1 scaffold protein and the Epl1 C-terminus that anchors the catalytic module to the NuA4 complex. In addition, I demonstrated that the Epl1 C-terminus and the Eaf1 HSA domain are the two key domains regulating the cellular equilibrium of NuA4 and picNuA4. Collectively, the work presented in the dissertation adds to our understanding of the interface between chromatin remodeling complexes, histone chaperones and histone variants in the regulation of chromatin biology and highlights the important role chromatin structure plays in basic cellular processes.

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Attribution-NonCommercial-NoDerivs 2.5 Canada