UC Merced

The BAF complex is an ATP dependent chromatin remodeling complex that is known to facilitate gene transcription. However, underlying mechanisms are not fully understood. We expected neuronal activity-induced gene transcription of delayed IEGs to require BAF complex-dependent chromatin remodeling and to be impaired when the latter functions sub-optimally, while rapid IEGs were expected to not need BAF as they already have accessible chromatin. Pharmacological inhibition or degradation of cBAF, but not the PBAF, and RNAi knockdown (KD) of nBAF subunit 170 and 53b significantly attenuated transcription of neuronal immediate early genes including rapid IEGs. BAF subunit KD didn’t alter phosphorylation of MAPK-ERK, a necessary signaling cascade for transcription. Also, pulse-chase with the nBAF inhibitor showed that the BAF complex is required for IEG transcription on a continuous basis. Taken together, using multiple experimental approaches, this is the first study to demonstrate a critical role of nBAF in neuronal activity-induced transcription.