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Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains


The ISWI family of ATP-dependent chromatin remodelers represses transcription by changing nucleosome positions. ISWI regulates nucleosome positioning by requiring a minimal length of extranucleosomal DNA for moving nucleosomes. ISW2 from Saccharomyces cerevisiae, a member of the ISWI family, has a conserved domain called SLIDE (SANT-like ISWI domain) that binds to extranucleosomal DNA ~19 base pairs from the edge of nucleosomes. Loss of SLIDE binding does not perturb binding of the ATPase domain or the initial movement of DNA inside of nucleosomes. Not only is extranucleosomal DNA required to help recruit ISW2, but also the interactions of the SLIDE domain with extranucleosomal DNA are functionally required to move nucleosomes.

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Figure 1: The SLIDE domain is required for ISW2 complex assembly.
Figure 2: Stable binding of the SLIDE domain to extranucleosomal DNA requires four conserved basic residues in SLIDE.
Figure 3: Binding of mSLIDE to nucleosomes is altered from that of WT.
Figure 4: The SLIDE domain is required for nucleosome movement and ATP hydrolysis.
Figure 5: The SLIDE domain helps move DNA into nucleosomes.
Figure 6: Certain regions in nucleosomal DNA are preferentially altered during remodeling by mSLIDE.
Figure 7: Stable binding of the SLIDE domain promotes the unidirectional movement of DNA exiting nucleosomes in ISW2 remodeling.
Figure 8: The actions of both the DNA translocase and SLIDE domains are required for moving nucleosomes, as shown in this model.

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We would like to thank N. Chatterjee for construction of the yeast strain for Isw2 catalytic subunit purification and members of the Bartholomew laboratory for their input. This work was funded by US National Institutes of Health GM 48413 (to B.B.) and the Howard Hughes Medical Institute (to X.Z.). S.D. is supported as a Merck Fellow of the Jane Coffin Childs Memorial Fund for Medical Research.

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S.K.H., S.K.B., S.D., X.Z. and B.B. designed experiments. S.K.H., S.K.B., S.D. and Y.L. performed experiments. S.K.H., S.D., X.Z. and B.B. wrote the paper.

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Correspondence to Blaine Bartholomew.

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Hota, S., Bhardwaj, S., Deindl, S. et al. Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains. Nat Struct Mol Biol 20, 222–229 (2013).

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