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

Area of Science:

• Molecular Biology
• Epigenetics
• Yeast Genetics

Background:

• Prions in Saccharomyces cerevisiae provide heritable responses to environmental changes via protein conformation propagation.
• Prion states ([PRION+]) may represent an atypical epigenetic control mechanism, but their link to the epigenome is unknown.
• Investigating connections between prion states and histone post-translational modifications (PTMs) is crucial for understanding prion function.

Purpose of the Study:

• To map the histone H3 modification landscape in yeast cells harboring [SWI+] and [PIN+] prion states.
• To determine if specific histone PTMs are associated with the presence or absence of these yeast prions.
• To explore the relationship between prion-induced epigenetic changes and canonical epigenetic pathways.

Main Methods:

• Comparative analysis of histone H3 modification levels (H3K36me2, H3K56ac, H3K4me3, H3K36me3, H3K79me3) in [SWI+] and [PIN+] yeast versus their prion-free ([swi-]) counterparts.
• Treatment of prion-containing yeast with guanidine hydrochloride to induce prion curing.
• Assessment of histone PTMs after prion curing to observe restoration to prion-free levels.

Main Results:

• The [SWI+] prion state is associated with decreased levels of H3K36me2 and H3K56ac.
• The [PIN+] prion state is linked to reduced levels of H3K4me3, H3K36me2, H3K36me3, and H3K79me3.
• Prion curing using guanidine hydrochloride restored histone PTMs to levels observed in prion-free yeast.

Conclusions:

• Yeast prion states ([SWI+] and [PIN+]) are distinctly correlated with specific alterations in histone H3 post-translational modifications.
• These prion-associated histone modifications differ from those observed in genetic loss-of-function models.
• The findings establish a novel link between yeast prion states and the histone modification landscape, providing new insights into prion-mediated epigenetic inheritance.