Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memory.
Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memory.
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DOI：
10.7554/elife.66454
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发表时间：
2021-09-02
期刊：
影响因子：
7.7
通讯作者：
Howard M
中科院分区：
文献类型：
--
作者：
Lövkvist C;Mikulski P;Reeck S;Hartley M;Dean C;Howard M
组蛋白修饰H3K27me3在polycomb介导的表观遗传沉默中起核心作用。H3K27me3招募并变变激活Polycomb suppression Complex 2 (PRC2)，将这种修饰添加到附近的组蛋白上，通过DNA复制提供一种读/写遗传机制。然而，对于一些PRC2靶点，纯粹基于组蛋白的表观遗传系统可能是不够的。我们在拟南芥的Polycomb靶开花位点C （FLC）上解决了这个问题，因为FLC内只有约3个核小体的狭窄成核区域介导了许多细胞周期的表观遗传状态转换和随后的记忆。为了解释记忆的意想不到的持久性，我们引入了一个数学模型，该模型结合了额外的蛋白质记忆存储元素，这些元素具有正反馈，除了组蛋白修饰外，还通过DNA复制在位点上持续存在。我们的混合模型解释了FLC表观遗传开关/记忆的许多特征，并封装了可能广泛适用的通用机制。
The histone modification H3K27me3 plays a central role in Polycomb-mediated epigenetic silencing. H3K27me3 recruits and allosterically activates Polycomb Repressive Complex 2 (PRC2), which adds this modification to nearby histones, providing a read/write mechanism for inheritance through DNA replication. However, for some PRC2 targets, a purely histone-based system for epigenetic inheritance may be insufficient. We address this issue at the Polycomb target FLOWERING LOCUS C (FLC) in Arabidopsis thaliana, as a narrow nucleation region of only ~three nucleosomes within FLC mediates epigenetic state switching and subsequent memory over many cell cycles. To explain the memory’s unexpected persistence, we introduce a mathematical model incorporating extra protein memory storage elements with positive feedback that persist at the locus through DNA replication, in addition to histone modifications. Our hybrid model explains many features of epigenetic switching/memory at FLC and encapsulates generic mechanisms that may be widely applicable.