Role for DNA polymerase α in epigenetic control of transcriptional silencing in fission yeast

In the fission yeast Schizosaccharomyces pombe, transcriptional silencing at the mating-type region, centromeres and telomeres is epigenetically controlled, and results from the assembly of higher order chromatin structures. Chromatin proteins associated with these silenced loci are believed to serve as molecular bookmarks that help promote inheritance of the silenced state during cell division. Specifically, a chromo-domain protein Swi6 is believed to be an important determinant of the epigenetic imprint. Here, we show that a mutation in DNA polymerase alpha (pol alpha) affects Swi6 localization at the mating-type region and causes a 45-fold increase in spontaneous transition from the silenced epigenetic state to the expressed state. We also demonstrate that pol alpha mutant cells are defective in Swi6 localization at centromeres and telomeres, Genetic analysis suggests that Pola and Swi6 are part of the same silencing pathway, Interestingly, we found that Swi6 directly binds to Pol alpha in vitro. Moreover, silencing-defective mutant Pol alpha displays reduced binding to Swi6 protein. This work indicates involvement of a DNA replication protein, Pol alpha, in heterochromatin assembly and inheritance of epigenetic chromatin structures.