HMGA regulates the global chromatin state and neurogenic potential in neocortical precursor cells

Abstract

Neural precursor cells (NPCs) in the mouse neocortex generate various neuronal and glial cell types in a developmental stage–dependent manner. Most NPCs lose their neurogenic potential during development, although the underlying mechanisms of this process are not fully understood. We found that the chromatin of mouse NPCs gradually becomes more condensed and less dynamic on a global scale during neocortical development. Furthermore, we found high mobility group A (HMGA) proteins to be essential for the open chromatin state of NPCs at early developmental stages. Knockdown of HMGA proteins in early-stage NPCs reduced their neurogenic potential. Conversely, overexpression of HMGA proteins conferred neurogenic potential on late-stage NPCs, an effect that was antagonized by coexpression of a histone H1 mutant that inhibits chromatin opening. Thus, HMGA proteins contribute to the neurogenic potential of NPCs in the early stages of neocortical development, possibly through induction of an open chromatin state.