Structural insights into histone binding and nucleosome assembly by chromatin assembly factor-1

Science. 2023 Aug 25;381(6660):eadd8673. doi: 10.1126/science.add8673. Epub 2023 Aug 25.


Chromatin inheritance entails de novo nucleosome assembly after DNA replication by chromatin assembly factor-1 (CAF-1). Yet direct knowledge about CAF-1's histone binding mode and nucleosome assembly process is lacking. In this work, we report the crystal structure of human CAF-1 in the absence of histones and the cryo-electron microscopy structure of CAF-1 in complex with histones H3 and H4. One histone H3-H4 heterodimer is bound by one CAF-1 complex mainly through the p60 subunit and the acidic domain of the p150 subunit. We also observed a dimeric CAF-1-H3-H4 supercomplex in which two H3-H4 heterodimers are poised for tetramer assembly and discovered that CAF-1 facilitates right-handed DNA wrapping of H3-H4 tetramers. These findings signify the involvement of DNA in H3-H4 tetramer formation and suggest a right-handed nucleosome precursor in chromatin replication.

MeSH terms

  • Chromatin
  • Chromatin Assembly Factor-1* / chemistry
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • Histones* / chemistry
  • Humans
  • Nucleosomes*
  • Protein Domains


  • Chromatin
  • Chromatin Assembly Factor-1
  • Histones
  • Nucleosomes