POL30(PCNA)的分析揭示了酿酒酵母亚端粒在瞬时抑制或双模式活性/沉默状态下的位置效应。

IF 4.2 2区 生物学 Q1 GENETICS & HEREDITY Epigenetics & Chromatin Pub Date : 2023-10-19 DOI:10.1186/s13072-023-00513-7
Safia Mahabub Sauty, Krassimir Yankulov
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引用次数: 0

摘要

背景:对果蝇位置效应变异的经典研究表明,与异染色质并列的基因存在双模态活动/沉默状态。后来用不可逆方法检测基因抑制的研究揭示了酿酒酵母和其他物种端粒的类似现象。在这项研究中,我们使用双报告基因构建体以及可逆和不可逆方法的组合,为PCNA和组蛋白伴侣蛋白在酿酒酵母亚端粒的稳定性和抑制状态的传播中的不同作用提供了证据。结果:我们显示了VIIL亚端粒报告基因的位置依赖性瞬时抑制或双模表达。我们还表明,复制钳POL30(PCNA)的突变或组蛋白伴侣CAF1或RRM3解旋酶的缺失会导致短暂的去抑制,而组蛋白伴侣ASF1的缺失则会导致从短暂的去压制转变为双模的抑制状态。我们分析了CAF1和RRM3与PCNA的物理相互作用,并讨论了这些发现对我们理解基因表观遗传状态的稳定性和传播的意义。结论:酿酒酵母端粒亚基存在不同的基因沉默模式,包括双模式和瞬时模式。我们描述了CAF1、RRM3和ASF1在这些基因抑制模式中的作用。我们建议,对过去和未来研究的解释应该考虑基因沉默的不同状态的存在。
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Analyses of POL30 (PCNA) reveal positional effects in transient repression or bi-modal active/silent state at the sub-telomeres of S. cerevisiae.

Background: Classical studies on position effect variegation in Drosophila have demonstrated the existence of bi-modal Active/Silent state of the genes juxtaposed to heterochromatin. Later studies with irreversible methods for the detection of gene repression have revealed a similar phenomenon at the telomeres of Saccharomyces cerevisiae and other species. In this study, we used dual reporter constructs and a combination of reversible and non-reversible methods to present evidence for the different roles of PCNA and histone chaperones in the stability and the propagation of repressed states at the sub-telomeres of S. cerevisiae.

Results: We show position dependent transient repression or bi-modal expression of reporter genes at the VIIL sub-telomere. We also show that mutations in the replicative clamp POL30 (PCNA) or the deletion of the histone chaperone CAF1 or the RRM3 helicase lead to transient de-repression, while the deletion of the histone chaperone ASF1 causes a shift from transient de-repression to a bi-modal state of repression. We analyze the physical interaction of CAF1 and RRM3 with PCNA and discuss the implications of these findings for our understanding of the stability and transmission of the epigenetic state of the genes.

Conclusions: There are distinct modes of gene silencing, bi-modal and transient, at the sub-telomeres of S. cerevisiae. We characterise the roles of CAF1, RRM3 and ASF1 in these modes of gene repression. We suggest that the interpretations of past and future studies should consider the existence of the dissimilar states of gene silencing.

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来源期刊
Epigenetics & Chromatin
Epigenetics & Chromatin GENETICS & HEREDITY-
CiteScore
7.00
自引率
0.00%
发文量
35
审稿时长
1 months
期刊介绍: Epigenetics & Chromatin is a peer-reviewed, open access, online journal that publishes research, and reviews, providing novel insights into epigenetic inheritance and chromatin-based interactions. The journal aims to understand how gene and chromosomal elements are regulated and their activities maintained during processes such as cell division, differentiation and environmental alteration.
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