The tale beyond the tail: histone core domain modifications and the regulation of chromatin structure

Abstract

Histone post-translational modifications occur, not only in the N-terminal tail domains, but also in the core domains. While modifications in the N-terminal tail function largely through the regulation of the binding of non-histone proteins to chromatin, based on their location in the nucleosome, core domain modifications may also function through distinct mechanisms involving structural alterations to the nucleosome. This article reviews the recent developments in regards to these novel histone modifications and discusses their important role in the regulation of chromatin structure.

Figure 1

Modifications of the nucleosome face. Histone post-translational modifications located on the nucleosome face may influence chromatin structure through multiple mechanisms. (A) These modifications might regulate chromatin–protein interactions in either a positive (top) or negative (bottom) fashion. (B) Alternatively, these modifications could affect higher order chromatin structure by altering interactions between neighboring nucleosomes. (C) Surface modifications are modeled on the crystal structure of the nucleosome (pdb file 1AOI) (10). The histone proteins are shown in a ribbon diagram with histone H2A shown in red, H2B in orange, H3 in blue and H4 in green. The DNA helix is shown in gray. Modified residues are depicted as spheres and colored yellow. Image was generated using the program Pymol.

Figure 2

Nucleosome lateral surface modifications. (A) Modifications to the lateral surface of the nucleosome are likely to influence chromatin structure through the modulation of histone–DNA interactions. (B) Modifications located at the nucleosome dyad axis are modeled on the nucleosome crystal structure. (C) Modifications near the DNA entry–exit points are highlighted on the nucleosome crystal structure. (D) Additional modifications near site of histone–DNA contact are shown on the nucleosome crystal structure. Crystal structure was rendered as described in the legend to Figure 1.

Figure 3

Modifications to regions of histone–histone interface. (A) Modifications located at points of contact between histone proteins may control chromatin structure through physical alterations in the nucleosome such as destabilization of tetramer–dimers interactions. (B) Locations of modifications in regions of histone–histone interface are depicted on the crystal structure of the nucleosome. Nucleosome was rendered as described in the legend to Figure 1.