Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis

Cell. 2004 Jan 9;116(1):51-61. doi: 10.1016/s0092-8674(03)01064-x.


Deposition of the major histone H3 (H3.1) is coupled to DNA synthesis during DNA replication and possibly DNA repair, whereas histone variant H3.3 serves as the replacement variant for the DNA-synthesis-independent deposition pathway. To address how histones H3.1 and H3.3 are deposited into chromatin through distinct pathways, we have purified deposition machineries for these histones. The H3.1 and H3.3 complexes contain distinct histone chaperones, CAF-1 and HIRA, that we show are necessary to mediate DNA-synthesis-dependent and -independent nucleosome assembly, respectively. Notably, these complexes possess one molecule each of H3.1/H3.3 and H4, suggesting that histones H3 and H4 exist as dimeric units that are important intermediates in nucleosome formation. This finding provides new insights into possible mechanisms for maintenance of epigenetic information after chromatin duplication.

Publication types

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

MeSH terms

  • Cell Cycle Proteins*
  • Chromatin Assembly Factor-1
  • Chromosomal Proteins, Non-Histone*
  • DNA / biosynthesis*
  • DNA Replication / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dimerization
  • Epigenesis, Genetic / genetics
  • HeLa Cells
  • Histone Chaperones
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Macromolecular Substances
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nucleosomes / genetics
  • Nucleosomes / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • CHAF1B protein, human
  • Cell Cycle Proteins
  • Chromatin Assembly Factor-1
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • HIRA protein, human
  • Histone Chaperones
  • Histones
  • Macromolecular Substances
  • Nuclear Proteins
  • Nucleosomes
  • Transcription Factors
  • DNA