The nucleosome is the hub of genetic activity in the nucleus of eukaryotes, which is why we are so interested in this 200 kDa complex of protein and DNA. The nucleosome is both a structurally and aesthetically beautiful macromolecule with an architecture that is complex to behold and yet elegant in its simplicity. This web page introduces the molecular architecture of the nucleosome to students of chromatin biology.
There are three principles which explain how the nucleosome is formed from the four core histones and 145-147 bp of DNA:
- the histone fold as a dimerization motif
- the four-helix bundle motif that allow H3/H4 dimers to form a tetramer and H2A/H2B to bind to the H3/H4 tetramer
- binding of DNA around the histone fold dimer crescent
Histone Fold as dimerization motif
The histone fold is comprised of a short helix (𝜶1), followed by a loop (L1), a longer helix (𝜶2), a second loop (L2) and another short helix (𝜶3). Each of the four cores histones (H3, H4, H2A, H2B) contain this histone fold structural motif. The histone fold is about 60 residues, or 50-60% of each full length core histone.
The histone fold is not a domain, i.e. it does not fold up on its own. It needs its partner histone fold to form a histone dimer. The H3 histone fold interacts with H4 histone fold to form a crescent like structure. The H2A and H2B histone folds form an analogous structure.
Histone Octamer
The H3/H4 heterodimers and the H2A/H2B heterodimers form an octamer using the four-helix bundle structural motif. The C-terminal region of histones H3 (𝜶2 C-terminus–L2–𝜶3) dimerize to form a four-helix bundle. This creates the H3/H4 tetramer. In an analogous manner, the C-terminal region of H2B heterodimerizes with the C-terminal region of H4 via a four-helix bundle to associate the H2A/H2B dimer with the H3/H4 tetramer. Binding one copy of the H2A/H2B dimer to the front side and one copy of the H2A/H2B dimer to the back side of the H3/H4 tetramer forms the histone octamer.
The non-histone fold portions of the core histones contribute to the histone tails and additional secondary structure elements such as the H3 𝜶N N-terminal helix and the H2B 𝜶C C-terminal helix (see right panel on figure just above). The histone tails are mobile and the specific orientation of the tails shown in this crystal structure reflects constraints imposed by crystal packing.
Nucleosome Core Particle
The nucleosome core particle wraps 145-147 bp of DNA around the histone octamer. The dyad of the nucleosome passes through a DNA base pair into the middle of the particle. The dyad corresponds to DNA superhelical location (SHL) 0 and the successive positions where the DNA minor groove faces the octamer are numbered -7 to +7.
The histone folds of each H3/H4 and H2A/H2B histone dimer bind approximately 28 bp of DNA. The crescent shaped histone dimer binds the minor groove of DNA through contacts with the
- 𝜶1-𝜶1 helices of the histone folds in the center of the crescent and
- L1-L2 loops of the histone folds at either ends of the crescent
Additional contacts to DNA are made by non-histone fold regions of the histones including histone tails and the H3 N-terminal helix.
You can find more information about the structure of the nucleosome in review articles in references 3 and 4 below, as well as in the primary references 1 and 2.
The figures on this page were created using PDB coordinates 1kx5 (ref. 2).
References
-
- Luger, K., A.W. Mader, R.K. Richmond, D.F. Sargent and T.J. Richmond (1997) Crystal structure of the nucleosome core particle at 2.8 Å resolution, Nature, 389:251-260.
- Davey, C.A., D.F. Sargent, K. Luger, A.W. Maeder and T.J. Richmond (2002) Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 Å resolution, J Mol Biol, 319:1097-1113.
- McGinty, R.K. and S. Tan (2014). Histones, Nucleosomes, and Chromatin Structure. In Fundamentals of Chromatin, J.L. Workman and S.M. Abmayr, ed (New York: Springer).
- McGinty, R.K, and S. Tan (2015). Nucleosome structure and function. Chem Reviews, 115:2255-2273.