Stability of a Human SWI-SNF Remodeled Nucleosomal Array

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Abstract
SWI-SNF alters DNA-histone interactions within a nucleosome in an ATP-dependent manner. These alterations cause changes in the topology of a closed circular nucleosomal array that persist after removal of ATP from the reaction. We demonstrate here that a remodeled closed circular array will revert toward its original topology when ATP is removed, indicating that the remodeled array has a higher energy than that of the starting state. However, reversion occurs with a half-life measured in hours, implying a high energy barrier between the remodeled and standard states. The addition of competitor DNA accelerates reversion of the remodeled array by more than 10-fold, and we interpret this result to mean that binding of human SWI-SNF (hSWI-SNF), even in the absence of ATP hydrolysis, stabilizes the remodeled state. In addition, we also show that SWI-SNF is able to remodel a closed circular array in the absence of topoisomerase I, demonstrating that hSWI-SNF can induce topological changes even when conditions are highly energetically unfavorable. We conclude that the remodeled state is less stable than the standard state but that the remodeled state is kinetically trapped by the high activation energy barrier separating it from the unremodeled conformation.