CREST functions as a molecular bridge between neuron-specific enhancers and epigenetic regulators in mature motor neurons

Then, CREST selectively recruits the CBP histone acetyltransferase to acetylate histone H3 lysine 27 at neuronal enhancers, leading to the epigenetic activation of mature neuronal genes through long-range chromatin interactions. We also show that CREST-bound enhancers gain accessibility through selective recruitment of the neuron-specific Brm ATPase during the transition from neural progenitors to mature motor neurons.

Furthermore, CREST knockout disrupts the expression of other subunits of neuronal BAF chromatin remodeling complexes, suggesting that CREST may influence the assembly of these complexes. Our findings reveal a non-canonical role of neuron-specific chromatin remodeling factors, demonstrating that CREST mediates communication between epigenetic regulators and neuron-specific enhancers, which are essential for proper neuronal function.