Emerging roles of linker histones in regulating chromatin structure and function

Nat Rev Mol Cell Biol. 2018 Mar;19(3):192-206. doi: 10.1038/nrm.2017.94. Epub 2017 Oct 11.


Together with core histones, which make up the nucleosome, the linker histone (H1) is one of the five main histone protein families present in chromatin in eukaryotic cells. H1 binds to the nucleosome to form the next structural unit of metazoan chromatin, the chromatosome, which may help chromatin to fold into higher-order structures. Despite their important roles in regulating the structure and function of chromatin, linker histones have not been studied as extensively as core histones. Nevertheless, substantial progress has been made recently. The first near-atomic resolution crystal structure of a chromatosome core particle and an 11 Å resolution cryo-electron microscopy-derived structure of the 30 nm nucleosome array have been determined, revealing unprecedented details about how linker histones interact with the nucleosome and organize higher-order chromatin structures. Moreover, several new functions of linker histones have been discovered, including their roles in epigenetic regulation and the regulation of DNA replication, DNA repair and genome stability. Studies of the molecular mechanisms of H1 action in these processes suggest a new paradigm for linker histone function beyond its architectural roles in chromatin.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromatin / chemistry
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism
  • DNA Repair
  • DNA Replication
  • Epigenesis, Genetic
  • Genetic Variation
  • Genomic Instability
  • Histones / chemistry
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Models, Biological
  • Models, Molecular
  • Nucleic Acid Conformation
  • Nucleosomes / chemistry
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Protein Conformation
  • Sequence Homology, Amino Acid


  • Chromatin
  • Histones
  • Nucleosomes
  • DNA