Page 26 - Academic Press Encyclopedia of Physical Science and Technology 3rd Molecular Biology

P1: GNH Revised Pages
Encyclopedia of Physical Science and Technology EN002G-104 May 17, 2001 20:53

818 Chromatin Structure and Modification

represented by a shorter dash, and between dimers—by a From a regulatory perspective, as shown in Fig. 6, a dra-
longer one): matic consequence of DNA winding onto the octamer is a
change in its accessibility to solution (and, by extension,
H2A–H2B—H4–H3—H3–H4—H2B–H2A
to nonhistone protein regulators). The obstacles are many
In vivo, of course, the histones are not arranged in linear in nature: the octamer itself obstructs the face of the DNA
fashion, but rather bundle together into a rather compact that is turned toward it, and—because of the proximity of
particle: the H3/H4 tetramer forms an inverted V (i.e., a the DNA gyres in the superhelix, one turn of the DNA
capital lambda, ), and the H2A/H2B heterodimers at- impedes access to the adjacent DNA turn. A great deal
tach to either side of the cleft at the bottom of this “ .” of experimental attention has been directed, therefore, to-
Viewed from the side, the resulting entity is shaped like a ward understanding how particular sequences bind to the
wedge (the octamer tapers toward the side of the H3/H4 histone octamer, and how specific regulators then bind to
tetramer). Yet another unfortunate consequence of text- nucleosomes containing their target sites.
book schematics is that the octamer is commonly repre- One important experimental variable in these assays
sented as a hockey puck—i.e., somewhat of a monolithic cannot, unfortunately, be seen in the X-ray crystal struc-
entity. The octamer is not a monolith—in fact, it is very ture: the NH 2 -terminal core histone tails account for ca.
clear that the heterodimerization interface between his- 25% of the histone mass, but are mostly unstructured in
tone H4 and histone H2B is a somewhat delicate one, the crystals. It is known that the tails of histones H2B and
and is amenable to disruption. Thus, a better analogy for H3 do not stick out to the side of the nucleosome, but
the octamer would be that of a Rubik’s cube—a three- rather emerge into solution between the gyres of the DNA
dimensional jigsaw puzzle—with individual components superhelix. The whereabouts of the histone H4 tail is un-
fitting together in a dynamic, pliable arrangement. clear (with the exception of a small segment that makes
Sixteen loop motifs decorate the sides of the octamer an internucleosomal contact in the crystal!).
side like rungs on a ladder, and these offer an interaction Attention to the tails’ structure is justified by their
interfacetotheDNA.Themajorityofcontactsbetweenthe prominence in regulatory phenomena that occur on chro-
histones and the DNA occur via hydrogen bonds and salt matin (Section IV.A). While normal nucleosome assembly
links to the phosphates in the DNA backbone, although can occur on tailless (proteolyzed) histones, normal tran-
two additional important sets of interactions occur when scriptional control can not—and the regulatory reach of
the side chain of arginine in the histone penetrates the mi- the tails can be illustrated by their sheer stereochemical
nor groove of the DNA, and when, remarkably, nonpolar reach (Fig. 8). Because the tails contain a combined 44 ly-
contacts are made with the deoxyribose. sine residues, at physiological pH they very likely coat the

FIGURE 8 The histone tails shown schematically to their full predicted length in relation to the nucleosome core
particle (drawn to scale).