DNA in the eukaryotic cell is packaged into a structure called chromatin. Chromatin is a dynamic structure that regulates access to DNA in response to environmental stimuli. Two widely conserved mechanisms that influence chromatin structure are the addition of post-translational modifications (PTMs) to histones and other chromatin-associated proteins, and the replacement of canonical histones with histone variants. Histone acetylation is catalyzed by histone acetyltransferases (HATs). HATs are comprised of a catalytic subunit, and associated proteins. Genetic analysis of the yeast HATs has shown that the combined deletion of the two HAT genes, GCN5 and SAS3, results in an inviable strain of yeast. In this thesis, I show that the inviability of the gcn5Δsas3Δ mutant is due to a combined failure to acetylate both histone H3 and the chromatin-remodeler protein Rsc4. Further, I show that acetylation of Rsc4 is catalyzed by Gcn5 in a HAT complex-independent manner. The linker histone, H1, is associated with higher-order chromatin structure; it has been shown that removal of H1 is required to allow access to DNA. In this work, I show that deletion of the linker histone rescues the growth of a conditional gcn5Δ sas3Δ mutant expressing a temperature-sensitive version of Sas3. Further, I present the incorporation of the histone variant Htz1 as an additional mechanism for mobilizing the linker histone away from the +1 nucleosome. I, also, provide data that corroborates evidence suggesting that the yeast linker histone binds a single nucleosome. Another histone variant found in many eukaryotes is histone H3.3, which is primarily incorporated into transcriptionally active regions in chromatin. In this dissertation, we created a series of human-yeast histone hybrids and tested their ability to rescue yeast lacking both endogenous copies of histone H3. Our data shows that the two human histone H3 variants, H3.1 and H3.3, are functionally interchangeable for growth in most nutrient conditions, confirming that the four amino acids that are different between H3.1 and H3.3 are not necessary to create transcriptionally permissive chromatin. Finally, we present evidence that three yeast H3 C-terminal domain amino acids play an important role in regulating the interactions of yeast H3.