This is achieved by successive levels of packaging of the DNA with proteins.^22 The first level is the winding
of DNA around a complex of basic proteins called histonesto form the nucleosome^23 (Figure 6.11, see also
Section 10.6.1). There are four different histone proteins in the nucleosome, Histones 2A, 2B, 3 and 4, and two
molecules of each are used in each nucleosome. The nucleosome has a flattened cylindrical structure, with two
turns of the DNA molecule around each monomer.^24 The nucleosomes themselves are wound again to form
a 30 nm fibre, which has a helical periodicity and which contains six nucleosomes per turn. Other proteins,
including different histones, participate in this second level of packaging. There are further levels of pack-
aging, which are poorly understood at present. The 30 nm fibre is drawn into looped domains, which are
condensed further into a 300 nm chromatin fibre. The familiar visible condensed chromosomes seen in
spreads of cells in metaphase (i.e., undergoing division) are further condensed from this (Section 2.6.1).
The packaging of DNA in chromatin has profound effects on gene expression. DNA that is tightly pack-
aged is inaccessible to the machinery for gene expression and ‘domains’ of similar gene expression, which
span multiple genes, are defined by particular boundary DNA elements and the protein complexes, which
bind to them. These effects of DNA packaging are covered below (Section 6.6.2).
Chromatin in cells fixed to microscope slides can be stained by a variety of compounds to reveal struc-
tural features related to the level of chromatin condensation. This kind of analysis is particularly revealing
when fully condensed chromosomes (in metaphase) that are about to undergo segregationinto daughter
cells are visualised (Figure 6.12a). Such analysis shows that certain regions of chromosomes are very
tightly wound into a dense structure, which is called heterochromatin. The regions surrounding centromeres
(see below) are often heterochromatic and other defined heterochromatic regions are characteristic to the
particular chromosomes containing them. Additionally, the Y-chromosomes of mammals are made up almost
entirely of heterochromatin. Heterochromatinwas long thought to be free of genes and to consist wholly
of non-coding highly repetitious DNA. We now know that genes do indeed reside in heterochromatin. For
example, the fine structure of the giant polytene chromosomes of Drosophila(Figure 6.12b), shows closely
Genes and Genomes 217
Figure 6.11 Nucleosomes and chromatin packing. Nucleosome proteins are shown as a disc with DNA wrapped
around. (a) The nucleosome. (b) The 30 nm fibre. (c) The 300 nm chromatin fibre