Chromatin remodeling by ISW2 and SWI/SNF requires DNA translocation inside the nucleosome


Chromatin-remodeling complexes regulate access to nucleosomal DNA by mobilizing nucleosomes in an ATP-dependent manner. In this study, we find that chromatin remodeling by SWI/SNF and ISW2 involves DNA translocation inside nucleosomes two helical turns from the dyad axis at superhelical location-2. DNA translocation at this internal position does not require the propagation of a DNA twist from the site of translocation to the entry/exit sites for nucleosome movement. Nucleosomes are moved in 9- to 11- or 50-base-pair increments by ISW2 or SWI/SNF, respectively, presumably through the formation of DNA loops on the nucleosome surface. Remodeling by ISW2 but not SWI/SNF requires DNA torsional strain near the site of translocation, which may work in conjunction with conformational changes of ISW2 to promote nucleosome movement on DNA. The difference in step size of nucleosome movement by SWI/SNF and ISW2 demonstrates how SWI/SNF may be more disruptive to nucleosome structure than ISW2.

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Figure 1: Movement of a DNA gap to 23 bp from the dyad axis interferes with nucleosomal mobilization by ISW2.
Figure 2: Single-nucleotide gaps and nicks in DNA near the dyad axis of the nucleosome interfered with nucleosome mobilization by ISW2.
Figure 3: DNA gaps block SWI/SNF remodeling when positioned 15–33 bp from the dyad.
Figure 4: Single-nucleotide gaps 18–33 bp from the dyad, but not DNA nicks, interfered with SWI/SNF remodeling in a strand-specific manner.
Figure 5: ISW2 moved nucleosomes in 9- and 11-bp increments, whereas SWI/SNF moved nucleosomes in 50-bp increments.
Figure 6: Models for nucleosome mobilization by ISW2 and SWI/SNF involving a DNA translocation-initiation step within the nucleosome.


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This work was supported by Public Health Service grants GM 48413 and GM 70864. We would like to thank M. Kagalwala (M.D. Anderson Cancer Center) for ISW2 and B. Zhang (Thomas University) for SWI/SNF and members of B.B.'s laboratory for helpful discussions.

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Correspondence to Blaine Bartholomew.

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Zofall, M., Persinger, J., Kassabov, S. et al. Chromatin remodeling by ISW2 and SWI/SNF requires DNA translocation inside the nucleosome. Nat Struct Mol Biol 13, 339–346 (2006).

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