Neuroepigenetics

This project aims to investigate how epigenetic mechanisms, specifically histone modifications, control gene expression during neuronal development and maturation. We recently discovered that histone bivalency, the simultaneous presence of two histone modifications with opposing functions, controls the timing of gene expression during the maturation of cerebellar neurons. In the proposed studies, we will examine the mechanisms and function of histone bivalency in the adult brain, as well as the species-specific differences in bivalency during mouse and human neuronal development. The research also aims to uncover the molecular mechanisms underlying neurodevelopmental diseases associated with mutations in EZH1, a key enzyme involved in the regulation of bivalent domains. This project will provide fundamental insights into the chromatin mechanisms of brain development and function, with potential implications for understanding and treating neurodevelopmental disorders.

How do neurons maintain their function throughout life? Neurons are born early in development and are not regenerated during an individual’s lifetime. Therefore, after maturation, our neurons must remain functional throughout life, which in humans can be up to a hundred years of more. The goal of my ERC Starting Grant 2024 proposal EpiNeuroLife was to uncover how the formation of the epigenetic landscape during neuronal maturation contributes to the maintenance of neuronal gene expression and function during adulthood and ageing. My preliminary studies show that developing neurons in the mouse cerebellum accumulate extremely high levels of the repressive histone modification H3K27me3 during maturation, which I hypothesise is critical for regulating chromatin compaction and neuronal gene expression later in life. In MOB3ERC113, I will generate supporting data for my ERC application to uncover the mechanisms of H3K27me3 deposition in neurons.