细胞表型差异性是胚胎干细胞自我更新群体的一个显著特征，基因表达噪声是这种异质性的重要来源。然而真核生物的基因表达受复杂的表观遗传调控，传统的基因表达随机性研究理论往往忽略了表观遗传机制，因此有待完善甚至重新阐述。为了解决这一问题，本项目拟结合小鼠胚胎干细胞在多潜能的维持以及定向分化过程中的实验观察和数据，集中研究组蛋白甲基化修饰对于基因表达随机动力学和细胞命运抉择机制的影响：理论上分析组蛋白甲基化修饰的热力学和动力学性质，阐述组蛋白甲基化修饰对于基因爆发式转录随机动力学的影响；应用上结合胚胎干细胞分化过程揭示组蛋白甲基化修饰在细胞命运抉择动力学中的关键作用。通过我们的工作，一方面理论上发展适合于多尺度多层次生物调节体系的统计物理新方法和动力学手段，另一方面相关方法也为实验研究表观遗传及基因转录行为提供理论解释和预测。

A remarkable feature of the self-renewing population of embryonic stem cells (ESCs) is their phenotypic heterogeneity. The stochastic noise in gene expression is an important source of this heterogeneity. However, eukaryotic genes are subject to complex epigenetic regulatory mechanisms. Transcription factors and chromatin modifying enzymes can control the random noise in gene expression. The traditional theory of stochastic gene expression often ignores this epigenetic regulation, therefore needs to be improved even to be re-elaborateed. In order to solve this problem in our project, we will study the effects of histone methylation on stochastic gene expression dynamics and cell fate decision mechanism for embryonic stem cells in mouse. We intend to combine the project with the experimental observation and data from the biochemcial processes of maintaining pluripotency and differentiation in embryonic stem cells. First, we will investigate theoretically the thermodynamic and kinetic properties of histone methylation modification, and clarify the roles of histone methylation on transcription bursting. Second,these methods developed above will be applied to the research of differentiation process in embryonic stem cell.We want to reveal the potential key role of histone methylation on cell fate decision dynamics. Through our work, on one hand, we will develop the statistical physics theory and nonlinear dynamics analysis method suitable to multi-scale multi-level biological regulation system. On the other hand, the related methods provides a theoretical basis for the experimental explanation and prediction about epigenetic and transcriptional behavior.