[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 Saccharomyces cerevisiae, 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.

Automated summary

In this study, the researchers explore the link between prion states and histone modifications in yeast. They find that different prion states are associated with specific changes in histone post-translational modifications. These findings provide novel insights into the function of prions in yeast.