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Cell. 2013 Jan 31;152(3):442-52. doi: 10.1016/j.cell.2012.12.040.

ISWI remodelers slide nucleosomes with coordinated multi-base-pair entry steps and single-base-pair exit steps.

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1
Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.

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.

PMID:
23374341
PMCID:
PMC3647478
DOI:
10.1016/j.cell.2012.12.040
[Indexed for MEDLINE]
Free PMC Article
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