Noncoding RNA-nucleated heterochromatin spreading is intrinsically labile and requires accessory elements for epigenetic stability
Noncoding RNA-nucleated heterochromatin spreading is intrinsically labile and requires accessory elements for epigenetic stability
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DOI：
10.7554/elife.32948
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发表时间：
2018-07-18
期刊：
影响因子：
7.7
通讯作者：
Al-Sady, Bassem
中科院分区：
文献类型：
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作者：
Greenstein, R. A.;Jones, Stephen K.;Al-Sady, Bassem
异染色质扩散反应是形成基因抑制结构的核心因素，这些结构在复制后以高位置精度或保真度重新建立。目前尚不清楚传播反应如何影响这种保真度。为了解决抑制基因稳定遗传的根源，我们使用一个定量描述活单细胞中传播反应的系统，探索了分裂酵母中传播事件的内在特征。我们证明了由非编码RNA核元件触发的传播是随机的、多峰的，并且随时间动态波动。这种稳定性的缺乏与组蛋白的高周转率有关。在交配型位点，这种不稳定的行为受到辅助顺式作用元件ReIII的限制，它抑制组蛋白的翻转。此外，REIII保护表观遗传记忆免受环境干扰。我们的结果表明，最普遍的传播类型，由非编码RNA核酸体驱动，在表观遗传上是不稳定的，需要与辅助元件合作才能达到高保真。
The heterochromatin spreading reaction is a central contributor to the formation of gene-repressive structures, which are re-established with high positional precision, or fidelity, following replication. How the spreading reaction contributes to this fidelity is not clear. To resolve the origins of stable inheritance of repression, we probed the intrinsic character of spreading events in fission yeast using a system that quantitatively describes the spreading reaction in live single cells. We show that spreading triggered by noncoding RNA-nucleated elements is stochastic, multimodal, and fluctuates dynamically across time. This lack of stability correlates with high histone turnover. At the mating type locus, this unstable behavior is restrained by an accessory cis-acting element REIII, which represses histone turnover. Further, REIII safeguards epigenetic memory against environmental perturbations. Our results suggest that the most prevalent type of spreading, driven by noncoding RNA-nucleators, is epigenetically unstable and requires collaboration with accessory elements to achieve high fidelity.