The role of BAF complexes in regulating transcription factor occupancy

Transcriptional regulation in humans involves extensive interplay between the ATP-dependent chromatin remodelling BAF complex and transcription factors, with the loss of BAF complex function having been shown to affect transcription factor occupancy. As mutations of BAF complex subunits present in over 20% of human cancers, with tumour suppressor subunits ARID1A and SMARCA4/2 being the most commonly mutated among them, investigating the context- specific effects of their mutations on transcription factor occupancy can give us much insight into the ensuing transcriptional changes that lead into oncogenic pathways. In this study, ChIP protocols were optimised for the transcription factors OCT4 and LEF1. Following the acute loss of ARID1A via AID degradation or inhibition of SMARCA4/2 via the BRM014 inhibitor across a time series, the effects on pioneer factor OCT4 occupancy were compared between conditions, determining OCT4 occupancy at some loci to be BAF complex- dependent. ARID1A loss was found to affect OCT4 occupancy at more loci than the SMARCA4/2 inhibition. Some loci were also observed to be affected only by SMARCA4/2 inhibition, but not by ARID1A loss. The time series data generated in this study contributes to the further characterisation of the direct and indirect effects on transcription factors and eventually, on the transcriptional responses relevant to the development of oncogenic pathways following specific BAF complex subunit inactivation or inhibition.