Unlocking the role of Enhancer of Polycomb Homolog 1 (EPC1) in brain function

Precise control of gene expression through epigenetic mechanisms is vital for proper brain development. Genetic variations affecting these epigenetic processes have been linked to various neurodevelopmental disorders characterized by intellectual disability and developmental delay. However, our understanding of the landscape of epigenetic factors orchestrating gene expression during brain development remains incomplete. Here, we investigate Epc1, a scaffold protein of the histone acetyltransferase complex NuA4/Tip60, whose role in the central nervous system remains unexplored. Using a knockout mouse model of EPC1 deficiency, we examine the spatial expression pattern of Epc1 in the mouse brain and its significance for brain function and cortical development. Our findings reveal that Epc1 is indispensable for cognitive function and organizational behavior, with negligible effects on locomotion or anxiety-related behaviors. Furthermore, Epc1 deficiency disrupts cortical excitability and neuronal migration in the cerebral cortex. These findings unveil the significance of Epc1 in brain function, highlighting its crucial involvement in the developmental trajectories of the cerebral cortex. In conjunction with clinical observations, this research provides valuable insights into the pathophysiological mechanisms underlying neurodevelopmental disorders.