The Folding of the Nucleosome Chain

The nucleosome is the fundamental unit of chromatin and has been introduced in Chapter 3. It consists of an octameric protein core composed of two copies each of histone proteins H2A, H2B, H3, and H4, and 145–147 base pairs (bp) of DNA. The DNA stably contacts the surface of the histone protein octamer core in a lefthanded superhelix of almost two turns. Histone proteins have a globular part formed by three well structured a-helices and the histone tails. These are long protruding N-terminal and H2A C-terminal extensions which lack a specific secondary structure. They are subject to post-translational modifications like acetylation, methylation, and phosphorylation at numerous sites, mostly in H3 and H4 (Chapter 4). While the core histones (or their variant forms) are stably bound to the DNA with residence times on the hour timescale, linker histone H1 and its avian counter part H5 associate more transiently with the nucleosome core particle and induce local conformational changes of the linker DNA [1–3]. As discussed in Chapters 3 and 5, the nucleosomal DNA is partly inaccessible to other protein factors, and the positioning of nucleosomes thus regulates the access to the DNA sequence. Similarly, the linker DNA between nucleosomes can be occluded by compacting the nucleosome chain, and a 50-fold difference in its accessibility to protein binding has been reported based on a comparison of dinucleosomes with a folded chain of 17 nucleosomes [4]. Thus, the organization of the nucleosome chain can regulate DNA access. The factors that determine this process as well as the resulting structures that form with chains of less than hundred nucleosomes are discussed in the present chapter. The organization of larger chromatin regions (i.e., thousands of nucleosomes and more) is covered in Chapters 9, 17, and 20. In numerous experiments it has been demonstrated that an extended chain of nucleosomes with B10 nm diameter can reversibly fold into fiber structures with a diameter of 20–40 nm at physiological salt concentrations [2, 3, 5]. This conformation has been termed the 30 nm chromatin fiber. Its structure remains controversially discussed, and various models for its conformation have been