ISWI Remodelers Slide Nucleosomes with Coordinated Multi-Base-Pair Entry Steps and Single-Base-Pair Exit Steps

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Cell (Impact Factor: 33.12). 01/2013; 152(3):442-52. DOI: 10.1016/j.cell.2012.12.040
Source: PubMed

ABSTRACT ISWI-family enzymes remodel chromatin by sliding nucleosomes along DNA, but the nucleosome translocation mechanism remains unclear. Here we use single-molecule FRET to probe nucleosome translocation by ISWI-family remodelers. Distinct ISWI-family members translocate nucleosomes with a similar stepping pattern maintained by the catalytic subunit of the enzyme. Nucleosome remodeling begins with a 7 bp step of DNA translocation followed by 3 bp subsequent steps toward the exit side of nucleosomes. These multi-bp, compound steps are comprised of 1 bp substeps. DNA movement on the entry side of the nucleosome occurs only after 7 bp of exit-side translocation, and each entry-side step draws in a 3 bp equivalent of DNA that allows three additional base pairs to be moved to the exit side. Our results suggest a remodeling mechanism with well-defined coordination at different nucleosomal sites featuring DNA translocation toward the exit side in 1 bp steps preceding multi-bp steps of DNA movement on the entry side.

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