Chromatin Mechanisms of Neuronal Fate Decisions

Fate specification and differentiation of Neural Stem Cells (NSCs) depend on the transcriptional silencing of alternative developmental programs. This process is determined by the cell type-specific regulation of transcriptional enhancers via chromatin modifications. However, how specific subsets of enhancers are silenced in NSCs and how this process controls neurogenesis and neuronal differentiation remain elusive. Here, we aim to discover the mechanisms of enhancer silencing by histone modifications and their role in neuronal fate decisions. It is known that the histone H3 lysine 9 (H3K9) methyltransferase PRDM16 is specifically expressed in NSCs of the mammalian cerebral cortex. PRDM16 regulates transcriptional enhancers and controls neurogenesis, neuronal fate specification, and migration in the developing mouse cortex. In this project, we combined a series of molecular, cellular, biochemical, and genomics approaches to elucidate the mechanism by which PRDM16 and its interacting partners regulate enhancers in the developing mouse cortex.