Dynamics and spatiotemporal organization of mammalian SWI/SNF chromatin remodeling complexes in transcriptional regulation

Abstract

ATP-dependent chromatin remodeling complexes play critical roles in the maintenance of tissue- and state-specific chromatin structure; however, the spatial organization and dynamics of these remodelers, as well as their relationship to active transcription remain unknown. Here, we leveraged a combination of live-cell single- molecule based imaging approaches coupled with genome-wide chromatin profiling studies to define the dynamics of each of the three mammalian SWI/SNF (mSWI/SNF) family of complexes. We find that mSWI/SNF complexes exhibit unique behaviors on chromatin in the form of localization and degree of dynamic, transient clustering in embryonic stem cells. Further, we find that such chromatin binding behaviors are dependent on catalytic activity and on the perturbation of complex-specific subunits. ATPase inhibition of mSWI/SNF complexes also results in the stabilization of RNA polymerase II (Pol II) condensates, suggesting a coupling of transcriptional and mSWI/SNF catalytic activity. Taken together, these findings reveal the dynamic nature at play for a major chromatin remodeling complex family and inform their functional roles in governing gene transcription.