Histone chaperones in nucleosome eviction and histone exchange

Abstract

The recent two years have led to the realization that histone chaperones contribute to the delicate balance between nucleosome assembly and re-assembly during transcription, and may in fact be involved as much in histone eviction as they are in chromatin assembly. Recent structural studies (in particular, the structure of an Asf1-H3/H4 complex) have suggested mechanisms by which this may be accomplished. The incorporation of various histone variants into nucleosomes has diverse effects on nucleosome structure, stability, and the ability of nucleosomal arrays to condense into chromatin higher order structures. It is likely that these seemingly independent ways to modify chromatin structure are interdependent.

Figure 1. Structure of the nucleosome (pdb code 1aoi)

DNA is shown in grey, H2A in yellow, H2B in red, H3 in blue, and H4 in green, respectively. Only one of the two H2A-H2B dimers is shown in each panel for clarity. The molecular two-fold axis dissecting the H3 four-helix bundle is indicated by a dashed line. Regions of interaction between the H2A-H2B dimer and the (H3-H4)₂ tetramer are indicated by solid ovals (left panel), whereas homotypic interactions between H3 or H2A are indicated by dashed ovals (right panel).

Figure 2. A summary of potential histone chaperone functions

The various functions of a chaperone are determined by the relative affinity of a chaperone for histones compared to the relative affinity of a histone bound to DNA. Both can be varied through posttranslational modifications of histones and / or chaperones, through sequence variations found in histone variants, and through the presence of other factors.

Figure 3. Histone chaperones share a β sheet motif, but otherwise exhibit no similarities in tertiary or quarternary structures

NAP1 (2ayu), Nucleoplasmin (1k5j)), Asf1 (1roc) and a homology model (1sq9) of HirA or CAF1 are shown as a ribbon diagram. Each monomer containing a four-stranded β sheet is represented as a gray triangles (bottom panel). In the homology model, the predicted 7 repeat domains within single peptideare shown with different colors and the best-matched 4 beta-sheet motif is in gray.

Figure 4. The disassembly of the DNA-bound (H3-H4)₂ tetramer by Asf1

The C-terminal β strand of H4 (magenta) undergoes a rotation to joins a β-sheet in Asf1. Tight interactions between the H3 α3 and α2 helices are incompatible with the four-helix bundle structure. The H2A-H2B dimers are omitted for clarity, and indeed may have to be removed prior to Asf1-mediated (H3-H4)₂ tetramer disassembly. Note that none of the regions of H3/H4 that interact with the DNA are occluded by Asf1.