Polycomb and Trithorax group proteins maintain stable epigenetic memory of gene expression states for some genes, but many targets show highly dynamic regulation. Here we combine experiment and theory to examine the mechanistic basis of these different modes of regulation. We present a mathematical model comprising a Polycomb/Trithorax response element (PRE/TRE) coupled to a promoter and including Drosophila developmental timing. The model accurately recapitulates published studies of PRE/TRE mediated epigenetic memory of both silencing and activation. With minimal parameter changes, the same model can also recapitulate experimental data for a different PRE/TRE that allows dynamic regulation of its target gene. The model predicts that both cell cycle length and PRE/TRE identity are critical for determining whether the system gives stable memory or dynamic regulation. Our work provides a simple unifying framework for a rich repertoire of PRE/TRE functions, and thus provides insights into genome-wide Polycomb/Trithorax regulation.

Polycomb 和 Trithorax 组蛋白对某些基因的基因表达状态保持稳定的表观遗传记忆，但许多目标表现出高度动态的调节。在这里，我们结合实验和理论来检验这些不同调节模式的机制基础。我们提出了一个数学模型，包括与启动子偶联的 Polycomb/Trithorax 响应元件 (PRE/TRE)，包括果蝇发育时机。该模型准确地概括了已发表的关于 PRE/TRE 介导的沉默和激活的表观遗传记忆的研究。通过最小的参数变化，相同的模型还可以概括不同 PRE/TRE 的实验数据，允许对其目标基因进行动态调节。该模型预测，细胞周期长度和 PRE/TRE 身份对于确定系统是否提供稳定记忆或动态调节至关重要。我们的工作为丰富的 PRE/TRE 功能提供了一个简单的统一框架，从而提供了对全基因组 Polycomb/Trithorax 调控的见解。