Sirtuins mediate cohesion of silenced domains in Saccharomyces cerevisiae

Abstract

Assembly of yeast heterochromatin requires Sir2, the founding member of an evolutionarily conserved family of NAD+‐dependent protein deacetylases known as the sirtuins. These enzymes play key roles as metabolic sensors involved in cellular lifespan, and they have been linked to cancer and numerous human diseases. Recently we uncovered an unanticipated function of yeast Sir2 within heterochromatin: the protein is both necessary and sufficient for cohesion of heterochromatic domains. Tethered Sir2 fragments mediate cohesion in the absence of other heterochromatic Sir proteins whereas synthetic heterochromatin domains that lack Sir2 do not mediate cohesion at all. We have mapped the domain of Sir2 that is responsible for cohesin enrichment at heterochromatic regions and we have identified point mutations in this domain that abolish heterochromatic cohesion. Here we show that these mutations bear little impact on heterochromatic repression in most standard phenotypic assays. However, we find that de novo establishment of silencing is delayed. These data suggest that cohesin regulates the assembly or functionalization of yeast heterochromatin. This research was supported by a grant from the NIH (GM51402).