Epigenetic pioneering by SWI/SNF family remodelers

In eukaryotic genomes, transcriptional machinery and nucleosomes compete for binding to DNA sequences; thus, a crucial aspect of gene regulatory element function is to modulate chromatin accessibility for transcription factor (TF) and RNA polymerase binding. Recent structural studies have revealed multiple modes of TF engagement with nucleosomes, but how initial “pioneering” results in steady-state DNA accessibility for further TF binding and RNA polymerase II (RNAPII) engagement has been unclear. Even less well understood is how distant sites of open chromatin interact with one another, such as when developmental enhancers activate promoters to release RNAPII for productive elongation. Here, we review evidence for the centrality of the conserved SWI/SNF family of nucleosome remodeling complexes, both in pioneering and in mediating enhancer-promoter contacts. Consideration of the nucleosome unwrapping and ATP hydrolysis activities of SWI/SNF complexes, together with their architectural features, may reconcile steady-state TF occupancy with rapid TF dynamics observed by live imaging.