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Nucleosome mobilization catalysed by the yeast SWI/SNF complex

Abstract

The generation of a local chromatin topology conducive to transcription is a key step in gene regulation1. The yeast SWI/SNF complex is the founding member of a family of ATP-dependent remodelling activities capable of altering chromatin structure both in vitro and in vivo2. Despite its importance, the pathway by which the SWI/SNF complex disrupts chromatin structure is unknown. Here we use a model system to demonstrate that the yeast SWI/SNF complex can reposition nucleosomes in an ATP-dependent reaction that favours attachment of the histone octamer to an acceptor site on the same molecule of DNA (in cis). We show that SWI/SNF-mediated displacement of the histone octamer is effectively blocked by a barrier introduced into the DNA, suggesting that this redistribution involves sliding or tracking of nucleosomes along DNA, and that it is achieved by a catalytic mechanism. We conclude that SWI/SNF catalyses the redistribution of nucleosomes along DNA in cis, which may represent a general mechanism by which ATP-dependent chromatin remodelling occurs.

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Figure 1: SWI/SNF displaces histones from DNA.
Figure 2: Octamer displaced by SWI/SNF is redistributed along the template.
Figure 3: SWI/SNF-mediated transfer of octamer is blocked by a barrier in cis.
Figure 4: Comparison of the stoichiometry required for SWI/SNF action in cis and in trans.

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Acknowledgements

We thank C. Peterson for pCL3; and D. Lilley, J. Allan and members of the Division of Gene Regulation, University of Dundee, for valuable discussion and support. This work was supported primarily by a Wellcome Trust Career Development Award to T.O.-H.; A.F. is an EMBO long-term fellow; I.W. is a BBSRC postgraduate student. A generous donation from the Rappaport Intermaritime Foundation was used to purchase imaging equipment.

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Correspondence to Tom Owen-Hughes.

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Whitehouse, I., Flaus, A., Cairns, B. et al. Nucleosome mobilization catalysed by the yeast SWI/SNF complex. Nature 400, 784–787 (1999). https://doi.org/10.1038/23506

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