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Establishment of heterochromatin in domain-size-dependent bursts [Genetics]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.412 ) Pub Date : 2021-04-13 , DOI: 10.1073/pnas.2022887118
Jan Fabio Nickels, Ashleigh Katrine Edwards, Sebastian Jespersen Charlton, Amanda Møller Mortensen, Sif Christine Lykke Hougaard, Ala Trusina, Kim Sneppen, Geneviève Thon

Methylation of histone H3K9 is a hallmark of epigenetic silencing in eukaryotes. Nucleosome modifications often rely on positive feedback where enzymes are recruited by modified nucleosomes. A combination of local and global feedbacks has been proposed to account for some dynamic properties of heterochromatin, but the range at which the global feedbacks operate and the exact mode of heterochromatin propagation are not known. We investigated these questions in fission yeast. Guided by mathematical modeling, we incrementally increased the size of the mating-type region and profiled heterochromatin establishment over time. We observed exponential decays in the proportion of cells with active reporters, with rates that decreased with domain size. Establishment periods varied from a few generations in wild type to >200 generations in the longest region examined, and highly correlated silencing of two reporters located outside the nucleation center was observed. On a chromatin level, this indicates that individual regions are silenced in sudden bursts. Mathematical modeling accounts for these bursts if heterochromatic nucleosomes facilitate a deacetylation or methylation reaction at long range, in a distance-independent manner. A likely effector of three-dimensional interactions is the evolutionarily conserved Swi6HP1 H3K9me reader, indicating the bursting behavior might be a general mode of heterochromatin propagation.



中文翻译:

依赖域大小的猝发中异染色质的建立[遗传]

组蛋白H3K9的甲基化是真核生物中表观遗传沉默的标志。核小体修饰通常依赖于正反馈,其中修饰的核小体会募集酶。提出了局部和全局反馈的组合来解决异染色质的一些动态特性,但是尚不清楚全局反馈的作用范围和异染色质传播的确切模式。我们在裂殖酵母中研究了这些问题。在数学建模的指导下,随着时间的推移,我们逐渐增加了交配型区域的大小并分析了异染色质的建立。我们观察到具有活性报道分子的细胞比例呈指数衰减,比率随域大小而降低。建立时期从野生型的几代到 在最长的区域中检查了200代,观察到位于成核中心外的两个报告基因高度相关的沉默。在染色质水平上,这表明各个区域在突然的突发中被静音。如果异色核小体以距离无关的方式促进远距离的脱乙酰化或甲基化反应,则数学模型会解释这些爆发。三维相互作用的一个可能的影响因素是进化上保守的Swi6 以与距离无关的方式。三维相互作用的一个可能的影响因素是进化上保守的Swi6 以与距离无关的方式。三维相互作用的一个可能的影响因素是进化上保守的Swi6HP1 H3K9me阅读器,表明爆发行为可能是异染色质繁殖的一般模式。

更新日期:2021-04-08
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