Sir3 and epigenetic inheritance of silent chromatin in Saccharomyces cerevisiae

Epigenetic mechanisms maintain the specific characteristics of differentiated cells by ensuring the inheritance of gene expression patterns through DNA replication and mitosis. In Saccharomyces cerevisiae, Sir protein-dependent gene silencing exhibits an epigenetic pattern of inheritance; once established the silenced domain is perpetuated mitotically from one generation to the next. To determine how silenced chromatin is perpetuated from generation to generation, we examined gene expression patterns and monitored the enrichment of molecular marks of silencing at the silent mating-type loci in conditions of limiting Sir3 protein. We observed that silencing at HMR, as previously reported for HML, is epigenetically inherited. This inheritance at the HMR locus is accompanied by an increased ability of previously silenced cells to retain or recruit limiting Sir3 protein to cis-acting silencer sequences (the HMR-E silencer). Interestingly, we also observed that the low H4-K16 histone acetylation and H3-K79 histone dimethylation associated with a silenced HMR locus persists in recently derepressed cells for several generations in levels of Sir3 insufficient to maintain these marks in long-term derepressed cells. The unique ability of previously silenced cells to retain Sir3 protein, maintain silencing-specific histone modifications, and repress HMR transcription at levels of Sir3 insufficient to mediate these effects in the long-term derepressed cells suggests that a cis-acting, chromatin-based mechanism drives inheritance of gene repression at this locus.