Mrc1Claspin is essential for heterochromatin maintenance in Schizosaccharomyces pombe

Genes Cells. 2024 Oct 29. doi: 10.1111/gtc.13175. Online ahead of print.

Abstract

In eukaryotes, maintenance of heterochromatin structure that represses gene expression during cell proliferation is essential for guaranteeing cell identity. However, how heterochromatin is maintained and transmitted to the daughter cells remains elusive. 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 for subtelomeric heterochromatin maintenance factors and identified 57 genes related to various cellular processes, in addition to well-characterized heterochromatin factors. 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 the pericentromeres and mating-type regions. Furthermore, we showed that Mrc1 is required for the localization of Snf2/Hdac-containing Repressor Complex (SHREC) and the maintenance of hypoacetylation state of histone H3K14. This study complements the recent discoveries that Mrc1 functions as a histone H3-H4 chaperone in heterochromatin maintenance.

Keywords: Mrc1; S. pombe; chromosome; heterochromatin.