Histone Octamer Structure Is Altered Early in ISW2 ATP-Dependent Nucleosome Remodeling

Cell Rep. 2019 Jul 2;28(1):282-294.e6. doi: 10.1016/j.celrep.2019.05.106.


Nucleosomes are the fundamental building blocks of chromatin that regulate DNA access and are composed of histone octamers. ATP-dependent chromatin remodelers like ISW2 regulate chromatin access by translationally moving nucleosomes to different DNA regions. We find that histone octamers are more pliable than previously assumed and distorted by ISW2 early in remodeling before DNA enters nucleosomes and the ATPase motor moves processively on nucleosomal DNA. Uncoupling the ATPase activity of ISW2 from nucleosome movement with deletion of the SANT domain from the C terminus of the Isw2 catalytic subunit traps remodeling intermediates in which the histone octamer structure is changed. We find restricting histone movement by chemical crosslinking also traps remodeling intermediates resembling those seen early in ISW2 remodeling with loss of the SANT domain. Other evidence shows histone octamers are intrinsically prone to changing their conformation and can be distorted merely by H3-H4 tetramer disulfide crosslinking.

Keywords: ISWI; SANT domain; chromatin remodeling; gene regulation; histones; nucleosome dynamics; nucleosome movement; nucleosome structure; transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Adenosine Triphosphate / metabolism
  • Catalytic Domain / genetics
  • Chromatin Assembly and Disassembly / genetics*
  • Computer Simulation
  • DNA Footprinting
  • Histones / chemistry
  • Histones / metabolism*
  • Mass Spectrometry
  • Models, Molecular
  • Nucleosomes / chemistry
  • Nucleosomes / metabolism*
  • Protein Binding
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Histones
  • ISWI protein
  • Nucleosomes
  • Transcription Factors
  • Adenosine Triphosphate
  • Adenosine Triphosphatases