Protein-Based Inheritance: Epigenetics beyond the Chromosome

Epigenetics refers to changes in phenotype that are not rooted in DNA sequence. This phenomenon has largely been studied in the context of chromatin modification. Yet many epigenetic traits are instead linked to self-perpetuating changes in the individual or collective activity of proteins. Most such proteins are prions (e. g., [PSI+], [URE3], [SWI+], [MOT3(+)], [MPH1(+)], [LSB+], and [GAR(+)]), which have the capacity to adopt at least one conformation that self-templates over long biological timescales. This allows them to serve as proteinbased epigenetic elements that are readily broadcast through mitosis and meiosis. In some circumstances, self-templating can fuel disease, but it also permits access to multiple activity states from the same polypeptide and transmission of that information across generations. Ensuing phenotypic changes allow genetically identical cells to express diverse and frequently adaptive phenotypes. Although long thought to be rare, protein- based epigenetic inheritance has now been uncovered in all domains of life.