10.6 DNA Packaging
10.6.1 Nucleosomes and Chromatin of the Eukaryotes
A typical eukaryotic cell contains roughly 2 metres of DNA, which must be compacted by a factor of 10^6
so as to fit within the nucleus. The DNA is assembled with proteins into complexes known as chromatin
(Section 6.4). The fundamental packaging unit of the eukaryotic DNA is the nucleosome, an octameric
complex of histone proteins and DNA (Figure 10.15). The histone octamer engages roughly one- and three-
quarter turns of duplex DNA in a left-handed toroidal superhelix. It has been proposed that the efficiency
of the histone-based system of packaging DNA was a key development in the expansion of the eukaryotic
genome, and the divergence of this branch of life.^39
The accessibility of DNA is determined primarily by the arrays of nucleosomes, which affect transcrip-
tion activity, mostly through repression. The cell has elaborate machinery to ‘re-model’ those arrays dur-
ing gene expression. Such machines transduce the free energy of ATP binding and hydrolysis to displace
nucleosomes. The machines are transiently fixed with respect to a target nucleosome, and it has been pro-
posed that they displace the DNA so that it twists up to form a loop that can move around the nucleosome,
causing the nucleosome to slide.^40 Modifications of the histones by acetylation and methylation provide
signals for recruitment of the remodelling machinery. Recently, it has also been discovered that variant
histones are used to mark boundaries for the repair of damaged DNA by recombination.
The crystal structure of the nucleosome has been solved at high resolution, from which one can observe
in detail the protein–protein and protein–DNA contacts that are made for a particular sequence of DNA
(Figure 10.15a). The histone octamer of the nucleosome is composed of two copies each of the four histone
proteins H2A, H2B, H3 and H4. These proteins have similar sequences, and have undoubtedly evolved by
gene duplication. Histones H3 and H4 are among the most highly conserved proteins in multi-cellular
eukaryotes, while H2A and H2B are comparatively more variable, especially at their termini. Histones H3
and H4 form a heterotypic dimer that self-pairs into a tetramer through a four-helix bundle, in which the
hydrophobic interfaces between helices intermesh in a ‘knobs-into-holes’ manner, just like the two-
stranded coiled-coil described for leucine zippers (Section 10.3.2).
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Figure 10.15 The nucleosome core particle (PDB: 1AOI). The histone amino termini protrude from the core
particle; these are sites of covalent modification that affect chromatin structure and gene regulation.
The histone dimers have been colour coded. (a) The dyad axis is vertical. (b) A side view: the dyad is
now in the plane of the page