NRSF gene regulatory network model. (A) NRSF in conjuction with CoREST and other corepressors prevents the transcription of several hundred targets, including neuronal splicing factors, transcription factors, and microRNAs, as well as many terminal differentiation genes in a stem cell. (B) Upon receiving neurogenic signals to terminally differentiate, the NRSF protein is degraded, which leads to derepression of its targets, which are now available to activators. In particular, the NRSE- associated miR-153, which is embedded in the pan-neuronal gene PTPRN that has a NRSE in one of its introns, is predicted to down-regulate both NRSF and CoREST mRNAs (which is also the predicted target of the NRSE-associated miR-29b and miR-124a), thus maintaining the derepression.
