What causes nucleosomes to stack so tightly on each other? Nucleosome-tonucleosome linkages that involve histone tails, most notably the H4 tail, constitute one important factor (Figure 4–29). Another important factor is an additional histone that is often present in a 1-to-1 ratio with nucleosome cores, known as Figure 4–28 A zigzag model for the 30histone H1. This so-called linker histone is larger than the individual core histones nm chromatin fiber. (A) The conformation of two of the four nucleosomes in a and it has been considerably less well conserved during evolution. A single his tetranucleosome, from a structure tone H1 molecule binds to each nucleosome, contacting both DNA and protein, determined by x-ray crystallography.  and changing the path of the DNA as it exits from the nucleosome. This change in (b) Schematic of the entire tetranucleosome; the exit path of DNA is thought to help compact nucleosomal DNA (Figure 4–30). the fourth nucleosome is not visible, being stacked on the bottom nucleosome and behind it in this diagram. (C) Diagrammatic illustration of a possible zigzag structure that could account for the 30-nm chromatin fiber. (A, PDb code: 1Zbb; C, adapted from C.l. woodcock, Nat. Struct. Mol. Biol. 12:639–640, 2005. with permission from macmillan Publishers ltd.)
Most eukaryotic organisms make several histone H1 proteins of related but quite distinct amino acid sequences. The presence of many other DNA-binding proteins, as well as proteins that bind directly to histones, is certain to add important additional features to any array of nucleosomes.
A gene is a nucleotide sequence in a DNA molecule that acts as a functional unit for the production of a protein, a structural RNA, or a catalytic or regulatory RNA molecule. In eukaryotes, protein-coding genes are usually composed of a string of alternating introns and exons associated with regulatory regions of DNA. A chromosome is formed from a single, enormously long DNA molecule that contains a linear array of many genes, bound to a large set of proteins. The human genome contains 3.2 × 109 DNA nucleotide pairs, divided between 22 different autosomes (present in two copies each) and 2 sex chromosomes. Only a small percentage of this DNA codes for proteins or functional RNA molecules. A chromosomal DNA molecule also contains three other types of important nucleotide sequences: replication origins and telomeres allow the DNA molecule to be efficiently replicated, while a centromere attaches the sister DNA molecules to the mitotic spindle, ensuring their accurate segregation to daughter cells during the M phase of the cell cycle.
The DNA in eukaryotes is tightly bound to an equal mass of histones, which form repeated arrays of DNA–protein particles called nucleosomes. The nucleosome is composed of an octameric core of histone proteins around which the DNA double helix is wrapped. Nucleosomes are spaced at intervals of about 200 nucleotide pairs, and they are usually packed together (with the aid of histone H1 molecules) into quasi-regular arrays to form a 30-nm chromatin fiber. Even though compact, the structure of chromatin must be highly dynamic to allow access to the DNA. There is some spontaneous DNA unwrapping and rewrapping in the nucleosome itself; however, the general strategy for reversibly changing local chromatin structure features ATP-driven chromatin remodeling complexes. Cells contain a large set of such complexes, which are targeted to specific regions of chromatin at appropriate times. The remodeling complexes collaborate with histone chaperones to allow nucleosome cores to be repositioned, reconstituted with different histones, or completely removed to expose the underlying DNA.