RUI: Elucidating epigenetic mechanisms for prion function in yeast

Prions are proteins that can adopt self-replicating conformations. In humans, prions are disease-causing agents, but in baker’s yeast prions may help the organism adapt to challenging environmental conditions. The mechanisms by which prions help yeast adapt are not fully understood. We have discovered a connection between gene organization and prions in baker’s yeast. We will investigate how prions engage gene organization mechanisms and impact cellular functions. This can lead to new knowledge in the fields of evolution and environmental adaptation. The educational objective of this proposal is to engage transfer students in mentored research, to support their success and progress along the STEM track. Prions are proteins that can adopt self-replicating conformations. Prions can cause phenotype alterations that can be inherited and allow for adaptation to shifting environments. Intriguingly, the way yeast prions engage cellular pathways has been poorly characterized. The research objective of this proposal involves the epigenomic landscape for the [PIN+] prion in the baker’s yeast Saccharomyces cerevisiae. While [PIN+] produces no evident phenotype, it is prevalent, naturally occurring and facilitates the formation of other prions. We have uncovered exciting connections between [PIN+] and canonical epigenetic mechanisms, such as histone post-translational modifications. Building upon this finding, we now seek to uncover the mechanisms linking [PIN+] to the epigenome and to identify the genes impacted by this link. This proposal aims to: (1) map changes in Histone H2A, H2B and H4 modifications associated with [PIN+], (2) determine the levels, localization and interactome of relevant histone modifying enzymes in [PIN+], and (3) define the genomic regions targeted by histone PTMs changes in [PIN+] Findings from Aim 3 will reveal specific cellular processes tied to [PIN+] and will allow for testing of undiscovered phenotypic advantages for [PIN+]. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.