DNA 过程因子 PCNA(POL30)的突变易导致 FLO11 基因座的表观遗传不稳定。

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Journal of cell science Pub Date : 2024-12-15 Epub Date: 2024-12-17 DOI:10.1242/jcs.262006
Safia Mahabub Sauty, Ashley Fisher, Andrew Dolson, Krassimir Yankulov
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引用次数: 0

摘要

在 S. cerevisiae 中,FLO 基因受到涉及组蛋白去乙酰化酶、转录因子和非编码 RNA 的异染色质形成的抑制。我们在此报告,加工因子 POL30(PCNA)的突变在亚端粒和交配型基因座上表现出短暂的去抑制作用,但不会去抑制 FLO 基因座。然而,复制体稳定因子 RRM3 和 TOF1 的缺失以及 pol30 突变会诱发絮凝表型。这些表型与 FLO11 启动子驱动的报告蛋白表达量增加、FLO11 的沉默→活性转换频率以及调控 lncRNA ICR1 和 PWR1 的表达量减少相关。FLO11局部复制景观的改变表明复制叉暂停与基因沉默的稳定性之间存在联系。在亚端粒和 HMLα 上对这些突变体的分析表明了类似的去抑制表型,并表明 FLO11 的活跃和沉默状态都存在短暂的不稳定性。我们的结论是,RRM3 和 TOF1 与 pol30 突变之间存在不同的相互作用,从而促进了 FLO11 的瞬时去抑制或完全表观遗传转换。我们认为,POL30、RRM3 和 TOF1 之间的相互作用对于维持所研究基因位点的表观遗传稳定性至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mutations in the DNA processivity factor POL30 predisposes the FLO11 locus to epigenetic instability in S. cerevisiae.

The FLO genes in Saccharomyces cerevisiae are repressed by heterochromatin formation, involving histone deacetylases, transcription factors and non-coding RNAs. Here, we report that mutations in the processivity factor POL30 (PCNA) that show transient derepression at the subtelomeres and the mating-type loci do not derepress FLO loci. However, deletions of the replisome stability factors RRM3 and TOF1 along with pol30 mutations induced flocculation phenotypes. The phenotypes correlated with increased expression of reporter proteins driven by the FLO11 promoter, the frequency of silent to active conversions of FLO11, and reduced expression of the regulatory long non-coding RNAs ICR1 and PWR1. Alterations in the local replication landscape of FLO11 indicate a link between defects in the fork protection complex and the stability of gene silencing. Analyses of these mutants at the subtelomeres and the HMLα locus showed a similar derepression phenotype and suggest transient instability of both active and silent states of FLO11. We conclude that RRM3 and TOF1 interact differentially with the pol30 mutations to promote transient derepression or complete epigenetic conversions of FLO11. We suggest that the interaction between POL30, RRM3 and TOF1 is essential to maintain epigenetic stability at the studied loci.

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来源期刊
Journal of cell science
Journal of cell science 生物-细胞生物学
CiteScore
7.30
自引率
2.50%
发文量
393
审稿时长
1.4 months
期刊介绍: Journal of Cell Science publishes cutting-edge science, encompassing all aspects of cell biology.
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