The chromatin-remodeling enzyme ACF is an ATP-dependent DNA length sensor that regulates nucleosome spacing

Nat Struct Mol Biol. 2006 Dec;13(12):1078-83. doi: 10.1038/nsmb1170. Epub 2006 Nov 12.

Abstract

Arrays of regularly spaced nucleosomes directly correlate with closed chromatin structures at silenced loci. The ATP-dependent chromatin-assembly factor (ACF) generates such arrays in vitro and is required for transcriptional silencing in vivo. A key unresolved question is how ACF 'measures' equal spacing between nucleosomes. We show that ACF senses flanking DNA length and transduces length information in an ATP-dependent manner to regulate the rate of nucleosome movement. Using fluorescence resonance energy transfer to follow nucleosome movement, we find that ACF can rapidly sample DNA on either side of a nucleosome and moves the longer flanking DNA across the nucleosome faster than the shorter flanking DNA. This generates a dynamic equilibrium in which nucleosomes having equal DNA on either side accumulate. Our results indicate that ACF generates the characteristic 50- to 60-base-pair internucleosomal spacing in silent chromatin by kinetically discriminating against shorter linker DNAs.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Chromatin / genetics*
  • Chromatin Assembly Factor-1
  • Chromatin Assembly and Disassembly / genetics*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA / genetics*
  • DNA / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Kinetics
  • Models, Biological
  • Nucleosomes / genetics*
  • Nucleosomes / metabolism

Substances

  • Chromatin
  • Chromatin Assembly Factor-1
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Nucleosomes
  • Adenosine Triphosphate
  • DNA