Mechanisms of Epigenetic Inheritance

表观遗传是一种以特定基因表达状态的遗传为特征，不改变DNA序列的现象。这种耐人寻味的遗传性模式与小RNA分子有关，但与表观遗传相关的分子机制仍然知之甚少。在前两轮资助中，我们已经确定了一些新的蛋白质，它们在生产在这些过程中起作用的小RNA分子方面发挥了重要作用。目前的建议建立在最近的发现基础上，这些发现指出了翻译后修饰的重要性，以及它们在调节生殖细胞相分离方面的潜在作用。相分离是一种物理现象，描述了混合物中分子的解混，在过去的几年里，这种过程在生物环境中越来越多地被观察到。事实上，我们多年来就已经知道，与表观遗传相关的小RNA驱动的过程与相分离结构密切相关，但这一相关性在很大程度上仍不清楚。目前很明显，这种相分离过程可能对功能很重要，但还不清楚如何发挥作用。我们已经确定了一些影响小RNA相关相分离的新蛋白质，目前的提议旨在更好地了解这些蛋白质如何相互作用，涉及哪种翻译后修饰，以及这些过程如何影响相分离，并最终由小RNA驱动的基因调控。

Epigenetic inheritance is a phenomenon that is characterized by the inheritance of a specific state of gene expression, without changes in DNA sequence. Small RNA molecules have been implicated in this intriguing mode of heritability, but the molecular mechanisms associated with epigenetic inheritance still remain poorly understood. In the previous two round of funding, we have identified a number of novel proteins that play important roles in the production of the small RNA molecules that act in these processes. The current proposal builds on recent findings, that point at the importance of post-translational modifications, and their potential role in regulating phase separation in germ cells. Phase separation is a physical phenomenon, describing the de-mixing of molecules in a mixture, and such processes have in the past years been increasingly observed in biological settings. Indeed, we have known for years that the small RNA-driven processes related to epigenetic inheritance are closely associated with phase-separated structures, but the relevance of this remained largely unclear. Presently it is clear that this phase separation process is likely important to function, but it is not yet clear how. We have identified a number of novel proteins that affect small RNA-related phase separation, and the current proposal aims to better understand how these proteins interact with each other, what sort of post-translational modifications are involved and how these processes affect phase separation, and ultimately small RNA driven gene regulation.