H2A-H2B dimer

The core unit of the chromatin, the nucleosome, consists of histones arranged as an octamer consisting of a (H3/ H4)2-tetramer complexed with two histone H2A/H2B dimers. Accessibility to DNA-binding proteins (for replication, repair, or transcription) is achieved by posttranslational modifications of the amino-termini of the histones, the histone tails phosphorylation, acetylation, methylation, ubiquitination, and sumoyla-tion. Especially acetylation of histone tails has been linked to transcriptional activation, leading to weakened interaction of the core complexes with DNA and subsequently to decondensation of chromatin. In contrast, deacetylation leads to transcriptional repression. As mentioned above, transcriptional coactivators either possess HAT activity or recruit HATs. HDACs in turn act as corepressors. 

Specifically, when histones are dissociated from DNA in 2 M NaCl, and H3 H4 tetramer and H2A-H2B dimer may be identified after fractionation of the histones at pH 5.0 and cross-linking with dimethylsu-berimidate (Komberg and Thomas, 1974). The inference was drawn that these complexes exist as such in the intact nucleosome. Furthermore, since both the un-cross-linked H3 H4 tetramer, and the uncross-linked H2A-H2B dimer are stable complexes, it has proved possible to characterize their physical properties in solution. Some of these results are summarized here. 

Although the quantitation of the cross-linking data is limited, as discussed above, comparison of the cross-linked histones obtained from chromatin with histone complexes obtained in the absence of DNA can help in developing a more detailed picture of histone-histone interactions. An H2A-H2B dimer was obtained by cross-linking of chromatin with short-range cross-linkers (for references, see Section... 

In arrays of closely packed nucleosomes composed of all four core histones, strands of H2A-H2B dimers could be incorporated in the grooves between the two H3-H4 strands, producing a four-stranded polymer. Alternatively, they could bind to the H3-H4 double-stranded fiber to give an octamer of the histones per nucleosome. This latter model is supported by the photochemical cross-linking of histones to DNA which have shown that within the nucleosome core the four core histones are not equivalently positioned with respect to... 

FKBP H2A-H2B (dimer) H3-H4 (tetramer) Histone chaperone regulating rDNA silencing... 

It is not widely appreciated that the major aspects of core histone interactions were well understood even before the development of the nucleosome model. Evidence for strong H2A H2B dimer interactions and an FI3 H4 tetramer was available in the early seventies (see Ref. [1], Chapter 2). By 1978, the rigorous sedimentation equilibrium studies from Moudrianakis laboratory had elucidated the thermodynamics of octamer formation [7]. What was missing, of course, was any structural information concerning these interactions. This was overcome by arduous X-ray diffraction studies, culminating in the elegantly detailed structures we have today [15,17,18], see also Flarp et al., this volume, p. 13. We now know how the core... 

Fig. 4. The functional subsets of the histone core, (a) (b) Ribbon Ca model of the H2A H2B dimer.

Fig. 16. Cacodylate binding site between NCP molecules. Figure shows details of the stacking interactions between two neighboring molecules involving the dorsal H3 H4 tetramer face of one NCP and the ventral H2A H2B dimer face an adjacent NCP. The acidic residues forming a surface patch on the dimer face are rendered in ball-and-stick. The H4 tail is in blue and the H3 region involved in the interaction is in yellow. The cacodylate is shown as a CPK rendering.

Fig. 17. Composite structural motions of subunits can be described with translation, libration, and screw-axis (TLS) analysis of the NCP. Analysis of the histone subunits are shown here, (a) Composite motion of histones H2A (blue) and H2B (blue) considered as individual elements and combined as H2A H2B dimer (red). Note for the individual histones that the axis of motion is parallel with the medial a-helix of the histone. The origin of the TLS axes are within the structural positions of the histone. The composite motion for the H2A H2B dimer is dominated by the motion of H2A, as is seen in the similarity of orientation and position of the two axes, (b) The orientation and motion of the two H2A H2B dimers appear symmetric across the dyad axis of the NCP. (c) H3 H4 composite motions when considered as dimers (blue) and as the tetramer (red). Interpretation is more complex because of the asymmetric magnitude of motion for the two dimers, and the different position in the axis of primary motion for the tetramer. These motions are most likely the consequence of packing interactions, described in greater detail in the text.

Ubiquitinated histones have been suggested to destabilize the interface between the H2A-H2B dimers and the H3-H4 tetramer [211], and to be depleted from highly condensed mitotic chromosomes and enriched in HI deficient chromatin [212]. In Drosophila, the inducible hsp70 and copia genes are ubiquitinated, which represents... 

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