Kawakami Kei, Ueno Yukari, Hayama Nao, Tanaka Katsunori
Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo, Japan.
Department of Biosciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Sanda, Hyogo, Japan.
Genes Cells. 2024 Dec;29(12):1207-1224. doi: 10.1111/gtc.13175. Epub 2024 Oct 29.
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 Mrc1, 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.
在真核生物中,维持异染色质结构对于保证细胞特性至关重要,这种结构在细胞增殖过程中会抑制基因表达。然而,异染色质是如何维持并传递给子细胞的仍不清楚。在本研究中,我们构建了一个报告系统来研究裂殖酵母(Schizosaccharomyces pombe)亚端粒区域异染色质的维持。我们证明,一旦亚端粒异染色质形成,它倾向于在细胞增殖过程中作为一种亚稳态结构得以维持。利用该系统,我们在粟酒裂殖酵母全基因组基因缺失文库中筛选亚端粒异染色质维持因子,除了已充分表征的异染色质因子外,还鉴定出57个与各种细胞过程相关的基因。我们聚焦于DNA复制检查点的介质Mrc1。我们发现,Mrc1不仅在亚端粒维持异染色质结构,在着丝粒周围区域和交配型区域也如此。此外,我们表明,Mrc1是含Snf2/组蛋白去乙酰化酶的阻遏复合物(SHREC)定位以及组蛋白H3K14低乙酰化状态维持所必需的。这项研究补充了最近关于Mrc1在异染色质维持中作为组蛋白H3 - H4伴侣发挥作用的发现。