Human SWI/SNF drives sequence-directed repositioning of nucleosomes on c-myc promoter DNA minicircles

The human SWI/SNF (hSWI/SNF) ATP-dependent chromatin remodeling complex is a tumor suppressor and essential transcriptional coregulator. SWI/SNF complexes have been shown to alter nucleosome positions, and this activity is likely to be important for their functions. However, previous studies have largely been unable to determine the extent to which DNA sequence might control nucleosome repositioning by hSWI/SNF complexes. Here, we employ a minicircle remodeling approach to provide the first evidence that hSWI/SNF moves nucleosomes in a sequence dependent manner, away from nucleosome positioning sequences favored during nucleosome assembly. This repositioning is unaffected by the presence of DNA nicks, and can occur on closed-circular DNAs in the absence of topoisomerases. We observed directed nucleosome movement on minicircles derived from the human hSWI/SNF-regulated c-myc promoter, which may contribute to the previously observed disruption of two promoter nucleosomes during c-myc activation in vivo. Our results suggest a model wherein hSWI/SNF-directed nucleosome movement away from default positioning sequences results in sequence-specific regulatory effects.