Computational and Systems Biology, John Innes Centre, Norwich Research Park, United Kingdom.
Cell and Developmental Biology, John Innes Centre, Norwich Research Park, United Kingdom.
Elife. 2021 Sep 2;10:e66454. doi: 10.7554/eLife.66454.
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 in , as a narrow nucleation region of only ~three nucleosomes within 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 and encapsulates generic mechanisms that may be widely applicable.
组蛋白修饰 H3K27me3 在 Polycomb 介导的表观遗传沉默中发挥核心作用。H3K27me3 招募并变构激活多梳抑制复合物 2（PRC2），后者将该修饰添加到附近的组蛋白上，为通过 DNA 复制进行遗传提供了读写机制。然而，对于一些 PRC2 靶标，纯粹基于组蛋白的表观遗传遗传机制可能是不够的。我们在 Polycomb 靶标 中解决了这个问题，因为 中只有大约三个核小体的狭窄成核区域介导了表观遗传状态的转换和随后的许多细胞周期的记忆。为了解释记忆的意外持久性，我们引入了一个数学模型，该模型包含了额外的蛋白质记忆存储元件，这些元件通过 DNA 复制在该基因座上持续存在，除了组蛋白修饰。我们的混合模型解释了 中表观遗传开关/记忆的许多特征，并封装了可能广泛适用的通用机制。
