In the transgenic animals, we targeted a hydrophobic domain of BAF53b. Further analysis will be necessary to fully understand how deletion of the hydrophobic domain impairs nBAF-mediated nucleosome remodeling. Nucleosome remodeling experiments are almost exclusively carried out in vitro and in cell culture, however nucleosome positioning experiments using high-density sequencing are emerging, which may make this more feasible in heterogeneous cell populations of various brain regions associated with learning and memory. In addition, currently available antibodies are insufficient to perform a chromatin immunoprecipitation making the localization of BAF53b to specific DNA binding sites unfeasible. It is also unclear how neuronal activity induced by a learning event activates nBAF-mediated nucleosome remodeling. In cultured neurons nBAF interacts with the calcium-regulated transcriptional activator Calcium-Response Transactivator (CREST)8. Calcium influx activates CREST-mediated transcription that is required for normal activity-dependent dendritic development48,49. In vitro, BAF53b is not required for the CREST-nBAF interaction, but loss of BAF53b does disrupt targeting of both nBAF and CREST to target gene promoters8. CREST expression in the hippocampus continues into adulthood48 and may serve as potential mechanism to link neuronal activity to nBAF mediated nucleosome remodeling.
