Cells contain dozens of different ATP-dependent chromatin remodeling complexes that are specialized for different roles. Most are large protein complexes that can contain 10 or more subunits, some of which bind to specific modifications on histones (see Figure 4–26C). The activity of these complexes is carefully controlled by the cell. As genes are turned on and off, chromatin remodeling complexes are brought to specific regions of DNA where they act locally to influence chromatin structure (discussed in Chapter 7; see also Figure 4–40, below).
Although some DNA sequences bind more tightly than others to the nucleosome core (see Figure 4–25), the most important influence on nucleosome positioning appears to be the presence of other tightly bound proteins on the DNA. Some bound proteins favor the formation of a nucleosome adjacent to them. Others create obstacles that force the nucleosomes to move elsewhere. The exact positions of nucleosomes along a stretch of DNA therefore depend mainly on the presence and nature of other proteins bound to the DNA. And due to the presence of ATP-dependent chromatin remodeling complexes, the arrangement of nucleosomes on DNA can be highly dynamic, changing rapidly according to the needs of the cell.
Although enormously long strings of nucleosomes form on the chromosomal DNA, chromatin in a living cell probably rarely adopts the extended “beads-on-astring” form. Instead, the nucleosomes are packed on top of one another, generating arrays in which the DNA is even more highly condensed. Thus, when nuclei are very gently lysed onto an electron microscope grid, much of the chromatin is seen to be in the form of a fiber with a diameter of about 30 nm, which is considerably wider than chromatin in the “beads-on-a-string” form (see Figure 4–21).
Figure 4–26 The nucleosome sliding catalyzed by ATP-dependent chromatin remodeling complexes. (A) Using the energy of ATP hydrolysis, the remodeling complex is thought to push on the DNA of its bound nucleosome and loosen its attachment to the nucleosome core. Each cycle of ATP binding, ATP hydrolysis, and release of the ADP and Pi products thereby moves the DNA with respect to the histone octamer in the direction of the arrow in this diagram. It requires many such cycles to produce the nucleosome sliding shown.
(b) The structure of a nucleosome-bound dimer of the two identical ATPase subunits (green) that slide nucleosomes back and forth in the ISw1 family of chromatin remodeling complexes. (C) The structure of a large chromatin remodeling complex, showing how it is thought to wrap around a nucleosome. modeled in green is the yeast RSC complex, which contains 15 subunits— including an ATPase and at least four subunits with domains that recognize specific covalently modified histones. (b, from l.R. Racki et al., Nature 462:1016–1021, 2009. with permission from macmillan Publishers ltd; C, adapted from
A.E. leschziner et al., Proc. Natl Acad. Sci. USA 104:4913–4918, 2007.) 192 Chapter 4:  DNA, Chromosomes, and genomes
How nucleosomes are organized into condensed arrays is unclear. The structure of a tetranucleosome (a complex of four nucleosomes) obtained by x-ray crystallography and high-resolution electron microscopy of reconstituted chromatin have been used to support a zigzag model for the stacking of nucleosomes in a 30-nm fiber (Figure 4–28). But cryoelectron microscopy of carefully prepared nuclei suggests that most regions of chromatin are less regularly structured.