GSE175529
Cooperation of chromatin remodeling SWI/SNF complex and pioneer factor AP1 shapes 3D enhancer landscapes [HiChIP]
The mechanism controlling the dynamic targeting of SWI/SNF has long been postulated to be coordinated by transcription factors (TFs), yet identifying and demonstrating the influence of different TFs has proven difficult. In this study we take a multi-omics approach to directly interrogate transient SWI/SNF interactors, chromatin targeting, and the plasticity of the resulting 3D epigenetic landscape. We utilized the novel proximity based labeling technique TurboID to identify the AP1 family as a critical interacting partner for endogenous SWI/SNF complexes. Validation through CUT&RUN profiling demonstrated SWI/SNF targeting enrichment at AP1 bound loci, and SWI/SNF – AP1 cooperation in chromatin targeting. Mapping of 3D chromatin structure via HiChIP revealed AP1-SWI/SNF dependent restructuring of promoter-enhancer architecture and generation of enhancer hubs, ultimately regulating transcription. Through direct interrogation of the SWI/SNF – AP1 interaction, we demonstrate a SWI/SNF functional dependency on AP1 mediated chromatin localization. We propose that pioneer factors such as AP1 bind and target SWI/SNF to inactive chromatin, where it restructures the genomic landscape into an active state through epigenetic rewiring spanning multiple dimensions. Overall design: Time course HiChIP profiling of K27Ac and ARID1A in inducible SMARCB1 G401 cell line