[PRION] States Are Associated with Specific Histone H3 Post-Translational Modification Changes.

Prions are proteins able to take on alternative conformations and propagate them in a self-templating process. In , prions enable heritable responses to environmental conditions through bet-hedging mechanisms. Hence, [PRION] states may serve as an atypical form of epigenetic control, producing heritable phenotypic change via protein folding. However, the connections between prion states and the epigenome remain unknown. Do [PRION] states link to canonical epigenetic channels, such as histone post-translational modifications? Here, we map out the histone H3 modification landscape in the context of the [SWI] and [PIN] prion states. [SWI] is propagated by Swi1, a subunit of the SWI/SNF chromatin remodeling complex, while [PIN] is propagated by Rnq1, a protein of unknown function. We find [SWI] yeast display decreases in the levels of H3K36me2 and H3K56ac compared to [swi] yeast. In contrast, decreases in H3K4me3, H3K36me2, H3K36me3 and H3K79me3 are connected to the [PIN] state. Curing of the prion state by treatment with guanidine hydrochloride restored histone PTM to [prion] state levels. We find histone PTMs in the [PRION] state do not match those in loss-of-function models. Our findings shed light into the link between prion states and histone modifications, revealing novel insight into prion function in yeast.