Mechanisms of Epigenetic Inheritance

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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.