Fig. 7.

A schematic illustration of NGF activation of KOR P2 during RA-induced neuronal differentiation of P19. In the absence of NGF, P2 is in a heterochromatin conformation marked by histone H3 K9 methylation (K9-me2). NGF can stimulate TrkA receptor and p75 NGFR. The p75 NGFR, but not TrkA, is induced in early differentiating P19, resulting in activation of intracellular signaling molecules such as Erk1/2, PLC, and PI3 kinase. In the P19 system, it is PI3 kinase pathway that is responsible for AP2β activation. Erk1/2 pathway is unclear, depicted with a question mark. PLC is not involved in AP2β. Activated AP2β increasingly binds to KOR P2, triggering epigenetic changes reflected by histone H3 K4 methylation (K4-me2), dissociation of HP1α and formation of RNA polII pre-initiation complex. KOR c is then actively transcribed in NGFR-expressing neurons.