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

The ISWI chromatin remodelers interact with extranucleosomal DNA to mediate nucleosome positioning. A new study now shows that the conserved SLIDE domain in the Isw2 subunit, which binds linker DNA, facilitates unidirectional linker DNA movement into nucleosomes. These findings suggest that the SLIDE domain functions in conjunction with the ATPase domain to mobilize nucleosomes. 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.