Histones: Gene Organisation and Post‐translational Modification

Abstract

Histones are highly conserved basic proteins that form the major part of the protein moiety of eukaryotic chromosomes. Together with deoxyribonucleic acid (DNA), they organise the repeat unit of chromatin, the nucleosome, which consists of a deoxyribonucleoprotein core particle and linker DNA connecting these core units. The core particle is composed of 147 nucleotide pairs of DNA and two copies of each of the four core histones H2A, H2B, H3 and H4. The DNA linking core particles is associated with one copy of a fifth histone type termed H1. The basal organisation of chromatin as a histone–DNA complex implies that histones functionally participate in the regulation of chromatin‐bound processes, such as transcription, DNA repair or DNA replication. Post‐translational modification of histone amino acid side chains or replacement of canonical histones by nonallelic variants and recognition of such modified sites by regulatory factors are key processes in modulating the functional organisation of chromatin.

Key Concepts:

  • The histone family of basic chromosome consists of five protein classes that organise together with DNA the nucleosome, the basic chromatin unit. Two copies of each of the four histones H2A, H2B, H3 and H4 form together with DNA the nucleosome core particle; linker DNA and histone H1 complete the nucleosome as the chromosomal repeat unit.

  • The five canonical histones are extremely conserved proteins, and the nucleosome structure is essentially the same from unicellular to vertebrate species.

  • Nonallelic variants of four of the five histones (the exception is H4) can replace the canonical isoforms, thereby mediating dynamic changes of chromatin structure and function.

  • Histones are post‐translationally modified by, for example, acetylation of lysine residues, methylation of lysine or arginine residues and phosphorylation of hydroxyl groups in side chains of serine, threonine or tyrosine. Such modified side chains (and combinations thereof) provide interaction sites for binding of factors involved in chromatin‐bound processes.

  • Histone H1 is also termed linker histones, because it interacts with the DNA linking nucleosome core particles. Yeast has just one type of H1‐like histones, whereas mammals have several nonallelic H1 variants. H1 is involved in the formation of higher order chromatin structures above the level of arrays of nucleosomes.

Keywords: histone; nucleosome; core particle; histone genes; phylogeny of histones; nonallelic variants; post‐translational modification; acetylation; methylation; phosphorylation

Figure 1.

Structural elements of linker and core histones. Each member of the five histone classes contains a globular region with a characteristic tertiary structure. The central domain of histone H1 consists of three α‐helices and a twisted antiparallel β‐structure. This structure was first derived from the globular domain of the avian H1 subtype H5 (Clark et al., ). It is very similar to the ‘winged helix’ DNA‐binding domain of several transcription factors (here indicated by grey shading). The globular portions of core histones contain characteristic histone‐fold domains. These are found in all four classes of core histones, they consist of three α‐helices (α1–α3, here shaded in grey) and the central (α2) helix provides the interface for dimerisation (H2A with H2B and H3 with H4) in forming the core histone octamer (for details and exact positions, see Luger et al., ). In addition to the histone fold forming α‐helices, histones H2A, H2B and H3 form additional, short α‐helices (here indicated in dark blue). The unstructured N‐terminal domains of the core histones are the main sites for post‐translational modifications, but these are also observed in the globular domains. Numbers indicate N‐ and C‐termini, borders of the winged helix domain in H1 and beginning of the α1‐helix of the histone‐fold motif. For details and core histone sequences, see Luger et al. (). H2A and H2B sequence lengths vary slightly from species to species. The drawings are based on X‐ray crystallography data of Clark et al. () and Luger et al. ().

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How to Cite close
Doenecke, Detlef(Apr 2014) Histones: Gene Organisation and Post‐translational Modification. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001154.pub2]