CAF-1-induced oligomerization of histones H3/H4 and mutually exclusive interactions with Asf1 guide H3/H4 transitions among histone chaperones and DNA

Nucleic Acids Res. 2012 Dec;40(22):11229-39. doi: 10.1093/nar/gks906. Epub 2012 Oct 2.


Anti-silencing function 1 (Asf1) and Chromatin Assembly Factor 1 (CAF-1) chaperone histones H3/H4 during the assembly of nucleosomes on newly replicated DNA. To understand the mechanism of histone H3/H4 transfer among Asf1, CAF-1 and DNA from a thermodynamic perspective, we developed and employed biophysical approaches using full-length proteins in the budding yeast system. We find that the C-terminal tail of Asf1 enhances the interaction of Asf1 with CAF-1. Surprisingly, although H3/H4 also enhances the interaction of Asf1 with the CAF-1 subunit Cac2, H3/H4 forms a tight complex with CAF-1 exclusive of Asf1, with an affinity weaker than Asf1-H3/H4 or H3/H4-DNA interactions. Unlike Asf1, monomeric CAF-1 binds to multiple H3/H4 dimers, which ultimately promotes the formation of (H3/H4)(2) tetramers on DNA. Thus, transition of H3/H4 from the Asf1-associated dimer to the DNA-associated tetramer is promoted by CAF-1-induced H3/H4 oligomerization.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromatin Assembly Factor-1 / chemistry
  • Chromatin Assembly Factor-1 / metabolism*
  • DNA / metabolism*
  • Histone Chaperones / chemistry
  • Histone Chaperones / metabolism*
  • Histones / chemistry
  • Histones / metabolism*
  • Models, Biological
  • Protein Binding
  • Protein Multimerization


  • Chromatin Assembly Factor-1
  • Histone Chaperones
  • Histones
  • DNA