ETV5 is Essential for Neuronal Differentiation of Human Neural Progenitor Cells by Repressing NEUROG2 Expression

Neural progenitor cells (NPCs) are multipotent cells that have the potential to produce neurons and glial cells in the neural system. NPCs undergo identity maintenance or differentiation regulated by different kinds of transcription factors. Here we present evidence that ETV5, which is an ETS transcription factor, promotes the generation of glial cells and drives the neuronal subtype-specific genes in newly differentiated neurons from the human embryonic stem cells-derived NPCs. Next, we find a new role for ETV5 in the repression of NEUROG2 expression in NPCs. ETV5 represses NEUROG2 transcription via NEUROG2 promoter and requires the ETS domain. We identify ETV5 has the binding sites and is implicated in silent chromatin in NEUROG2 promoter by chromatin immunoprecipitation (ChIP) assays. Further, NEUROG2 transcription repression by ETV5 was shown to be dependent on a transcriptional corepressor (CoREST). During NPC differentiation toward neurons, ETV5 represses NEUROG2 expression and blocks the appearance of glutamatergic neurons. This finding suggests that ETV5 negatively regulates NEUROG2 expression and increases the number of GABAergic subtype neurons derived from NPCs. Thus, ETV5 represents a potent new candidate protein with benefits for the generation of GABAergic neurons.