Mrc1Claspin is essential for heterochromatin maintenance in Schizosaccharomyces pombe

Abstract

Heterochromatin is a highly condensed chromatin structure that represses gene expression. In eukaryotes, maintenance of the heterochromatin structure during cell proliferation is essential for guaranteeing cell identity. However, how heterochromatin is maintained and transmitted to the daughter cells remains largely unknown. In this study, we constructed a reporter system to study the maintenance of heterochromatin in the subtelomeric region of the fission yeast, Schizosaccharomyces pombe. We demonstrated that once subtelomeric heterochromatin was established, it tended to be maintained as a metastable structure through cell proliferation. Using this system, we screened an S. pombe genome-wide gene deletion library and identified 57 factors required for the maintenance of subtelomeric heterochromatin. We focused on Mrc1Claspin, a mediator of DNA replication checkpoint. We found that Mrc1 maintains heterochromatin structure not only at the subtelomeres but also at other heterochromatic loci, such as the pericentromeres and mating-type regions. Furthermore, we showed that Mrc1 facilitates the hypoacetylation state of histone H3K14 by recruiting the Snf2/Hdac-containing Repressor Complex (SHREC), via physical interaction. In addition, depletion of Mst2, an H3K14 acetyltransferase, restored heterochromatin integrity in mrc1 mutants. This is the first report to show a link between DNA replication factors and H3K14 deacetylation in heterochromatin.