DNA复制过程中由随机组蛋白标记丢失导致的表观遗传切换理论
Theory of epigenetic switching due to stochastic histone mark loss during DNA replication
AI总结：
本文提出了一种混合随机-确定性框架，用于计算由DNA复制过程中随机组蛋白标记丢失驱动的表观遗传切换速率，该框架能解析推导切换速率并解释实验数据，为定量研究表观遗传遗传提供了重要工具。
摘要：
除了遗传序列外，一个细胞从其祖先那里继承了了多少信息？哪些表观遗传机制允许了这一点？尽管可用的表观遗传数据不断增加，但这种信息如何通过细胞周期进行遗传仍未被完全理解。通常，表观遗传标记可以表现出双稳态行为，其双稳态通过细胞周期传递给子细胞，为细胞提供了一种记忆形式。然而，记忆丢失事件也会发生，即子细胞发生表观遗传状态切换（相对于母细胞）。在这里，我们开发了一个框架来计算这些表观遗传切换速率，适用于由DNA复制驱动的情况，即由于复制导致的记忆丢失事件的频率。我们确定性地考虑细胞周期中组蛋白修饰的动态，但在DNA复制时除外，此时核小体在两条子DNA链之间随机分布，因此是随机实现的。这种混合随机-确定性方法能够解析推导复制驱动的切换速率。在保持极大简单性的同时，该框架可以解释实验切换速率数据，确立了其作为定量研究表观遗传遗传框架的生物学重要性。
英文摘要：
How much information does a cell inherit from its ancestors beyond its genetic sequence? What are the epigenetic mechanisms that allow this? Despite the rise in available epigenetic data, how such information is inherited through the cell cycle is still not fully understood. Often, epigenetic marks can display bistable behaviour and their bistable state is transmitted to daughter cells through the cell cycle, providing the cell with a form of memory. However, loss-of-memory events also take place, where a daughter cell switches epigenetic state (with respect to the mother cell). Here, we develop a framework to compute these epigenetic switching rates, for the case when they are driven by DNA replication, i.e., the frequency of loss-of-memory events due to replication. We consider the dynamics of histone modifications during the cell cycle deterministically, except at DNA replication, where nucleosomes are randomly distributed between the two daughter DNA strands, which is therefore implemented stochastically. This hybrid stochastic-deterministic approach enables an analytic derivation of the replication-driven switching rate. While retaining great simplicity, this framework can explain experimental switching rate data, establishing its biological importance as a framework to quantitatively study epigenetic inheritance.
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