Abstract Embryonic development depends on spatially and temporally orchestrated gene regulatory networks. Expressed in neural stem and progenitor cells (NSPCs), the transcription factor sex-determining region Y box 2 (Sox2) is critical for embryogenesis and stem cell maintenance in neural development. Whereas Sox2 is regulated by a distal cluster of enhancers in embryonic stem cells (ESCs), enhancers closer to the gene have been implicated in Sox2 transcriptional regulation in the neural lineage.