From chromatin dynamics to brain disease: Polycomb-Trithorax mechanisms in neurodevelopment.

Neurogenesis requires precise coordination of gene expression, a process governed by the Polycomb (PcG) and Trithorax (TrxG) group proteins. In this review, we discuss how these proteins balance stem cell maintenance with neuronal differentiation and how the disruption of these processes may contribute to neurodevelopmental disorders and pediatric brain tumors. Recent studies have uncovered how PcG-TrxG dynamics and poised/bivalent chromatin states regulate developmental timing and lineage choice. Dysregulation of these epigenetic dynamics perturbs neuronal maturation and can drive aberrant developmental programs in pediatric brain disorders. These insights reveal how PcG-TrxG imbalance alters developmental trajectories and links chromatin dysregulation to disease. These epigenetic pathways are promising therapeutic targets for neurodevelopmental disorders and pediatric brain tumors.