The Interaction of DNA with the Histone Octamer Is Dynamic
As we will learn in detail in Chapter 17, the incorporation of DNA into nucleosomes can have a profound impact on the expression of the gennme. In many instances it is critical that nucleosomes can be moved or that their grip on the DNA can be loosened to allow access to particular regions of DNA. Consistent with this requirement, the association of the histone octamer with Ihe DNA is inherently dynamic. In addition, there are factors that act on the nucleosome to increase or decrease the dynamic nature of this association. Together, these properties allow changes in nucleosome position and DNA association in response to the frequently changing needs for DNA accessibility.
Like all interactions mediated by noncovalent bonds, the association of any particular region of DNA with the histone octamer is not permanent: any individual region of the DNA will transiently be released from figure 7-34 A mode) for gaining access to nucicosome-associated DNA.
Studies of the ability of sequence-specific DNA binding proteins to bind niideosomes suggest that unwrapping of the DNA from the nudeo some is responsible for accessibility of the DNA. Thus, DNA sites dosest to the entry and exu points are the most acoessibfe and sites closest to the midpoint of the bound DNA are least accessible.
tight interaction with the octamer now and then. This release is analogous to the occasional opening of the DNA double helix (as we discussed in Chapter 6). The dynamic nature of DNA binding to the histone core structure is important, because many DNA-binduig proteins strongly prefer histone-free DNA. Such proteins can only recognize their binding site when it is released from the histone octamer or is contained in linker or nuclcosome-free DNA. As a result of intermittent, spontaneous unwrapping of DNA from the nucleosome, a protein ran gain access to its DNA-binding sites with a probability of 1 in 1,000 to 1 in 100.000, depending on where the binding site is within the nucleosome. The more central the binding site, the less frequently it is accessible. Thus, a binding site near position 73 of the 147 base pairs tightly associated with a nucleosome is least frequently accessible, whereas binding sites near the ends (positions 1 or 147} of the nucleosomal DNA are most frequently accessible. These findings indicate that the mechanism of ex-fxisure is due to unwrapping of the DNA from the nudeosome, rather than to the DNA briefly coming off the surface of the histone octamer (Figure 7-34), It is important to note that these studies were performed on a population of individual nuclcosoines in a test lube: the ability of DNA to unwrap from the nucleosome may be different for the large nucleosomal arrays in the cell.
Nucleosome Remodeling Complexes Facilitate Nucleosome Movement
The stability of the histone octamer-DNA interaction is influenced by large protein complexes referred to as nucleosome remodeling complexes. These multi-protein, complexes facilitate changes in nucleosome location or interaction with the DNA using the energy of ATP hydrolysis. These changes can come in three flavors: (1) "sliding" of the histone octamer along the DNA [Figure 7-35a), (2) the complete "transfer" of a histone octamer from one DNA molecule to another (Figure 7-35b), or (3) the "remodeling" of the nucleosome to allow increased access to the DNA (Figure 7-3Sc).
a sliding b transfer
FIGURE 7-35 Nucleosome movement catalyzed by nudeosome remodeling activities, (a) Nudeosome movement by slid ing along a DNA molecule exposas sites for DNA binding proteins, (b) Nudeosome movement can alternatively occur by transfer ol the nudeosome from one strand ol DNA to another, (c) Remodeling allows association of a DNA-binding protein without altering its position on DNA.
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