The interface between DNA and histone is extensive: 142 hydrogen bonds are formed between DNA and the histone core in each nucleosome. Nearly half of these bonds form between the amino acid backbone of the histones and the sugar-phosphate backbone of the DNA. Numerous hydrophobic interactions and salt linkages also hold DNA and protein together in the nucleosome. More than one-fifth of the amino acids in each of the core histones are either lysine or arginine (two amino acids with basic side chains), and their positive charges can effectively
Figure 4–22 Structural organization of the nucleosome. A nucleosome contains a protein core made of eight histone molecules. In biochemical experiments, the nucleosome core particle can be released from isolated chromatin by digestion of the linker DNA with a nuclease, an enzyme that breaks down DNA. (The nuclease can degrade the exposed linker DNA but cannot attack the DNA wound tightly around the nucleosome core.) After dissociation of the isolated nucleosome into its protein core and DNA, the length of the DNA that was wound around the core can be determined. This length of 147 nucleotide pairs is sufficient to wrap 1.7 times around the histone core.
Figure 4–21 Nucleosomes as seen in the electron microscope. (A) Chromatin isolated directly from an interphase nucleus appears in the electron microscope as a thread about 30 nm thick. (b) This electron micrograph shows a length of chromatin that has been experimentally unpacked, or decondensed, after isolation to show the nucleosomes. (A, courtesy of barbara Hamkalo; b, courtesy of victoria Foe.) core histones linker DNA of nucleosome “beads-on-a-string” nucleosome includes form of chromatin ~200 nucleotide pairs of DNA
Figure 4–23 The structure of a nucleosome core particle, as determined by x-ray diffraction analyses of crystals. Each histone is colored according to the scheme in Figure 4–22, with the DNA double helix in light gray. (Adapted from k. luger et al., Nature 389:251–260, 1997. with permission from macmillan Publishers ltd.) neutralize the negatively charged DNA backbone. These numerous interactions explain in part why DNA of virtually any sequence can be bound on a histone octamer core. The path of the DNA around the histone core is not smooth; rather, several kinks are seen in the DNA, as expected from the nonuniform surface of the
Figure 4–24 The overall structural organization of the core histones. (A) Each of the core histones contains an N-terminal tail, which is subject to several forms of covalent modification, and a histone fold region, as indicated. (b) The structure of the histone fold, which is formed by all four of the core histones. (C) Histones 2A and 2b form a dimer through an interaction known as the “handshake.” Histones H3 and H4 form a dimer through the same type of interaction. (D) The final histone octamer on DNA. Note that all eight N-terminal tails of the histones protrude from the disc-shaped core structure. Their conformations are highly flexible, and they serve as binding sites for sets of other proteins.
core. The bending requires a substantial compression of the minor groove of the DNA helix. Certain dinucleotides in the minor groove are especially easy to compress, and some nucleotide sequences bind the nucleosome more tightly than others (Figure 4–25). This probably explains some striking, but unusual, cases of very precise positioning of nucleosomes along a stretch of DNA. However, the sequence preference of nucleosomes must be weak enough to allow other factors to dominate, inasmuch as nucleosomes can occupy any one of a number of positions relative to the DNA sequence in most chromosomal regions.