Histone chaperones FACT and Spt6 prevent histone variants from turning into histone deviants

Bioessays. 2016 May;38(5):420-6. doi: 10.1002/bies.201500122. Epub 2016 Mar 15.


Histone variants are specialized histones which replace their canonical counterparts in specific nucleosomes. Together with histone post-translational modifications and DNA methylation, they contribute to the epigenome. Histone variants are incorporated at specific locations by the concerted action of histone chaperones and ATP-dependent chromatin remodelers. Recent studies have shown that the histone chaperone FACT plays key roles in preventing pervasive incorporation of two histone variants: H2A.Z and CenH3/CENP-A. In addition, Spt6, another histone chaperone, was also shown to be important for appropriate H2A.Z localization. FACT and Spt6 are both associated with elongating RNA polymerase II. Based on these two examples, we propose that the establishment and maintenance of histone variant genomic distributions depend on a transcription-coupled epigenome editing (or surveillance) function of histone chaperones.

Keywords: CENP-A; CenH3; Cse4; FACT; H2A.Z; Psh1; SWR-C; Spt16; Spt6; histone chaperone; histone variant; ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / genetics
  • Autoantigens / metabolism
  • Centromere Protein A
  • Chromatin Assembly and Disassembly
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA Methylation
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Epigenesis, Genetic*
  • High Mobility Group Proteins / genetics*
  • High Mobility Group Proteins / metabolism
  • Histone Chaperones / genetics*
  • Histone Chaperones / metabolism
  • Histones / genetics*
  • Histones / metabolism
  • Humans
  • Nucleosomes
  • Protein Processing, Post-Translational*
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription, Genetic
  • Transcriptional Elongation Factors / genetics*
  • Transcriptional Elongation Factors / metabolism


  • Autoantigens
  • CENPA protein, human
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • FACT protein, S cerevisiae
  • High Mobility Group Proteins
  • Histone Chaperones
  • Histones
  • Htz1 protein, S cerevisiae
  • Nucleosomes
  • SPT6 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcriptional Elongation Factors
  • RNA Polymerase II