Nucleosome spacing

Blank, T.A. and Becker, P.B. (1995) Electrostatic mechanism of nucleosome spacing. J. Mol. Biol. 

Kleinschmidt, J.A. and Steinbeisser, H. (1991) DNA-dependent phosphorylation of histone H2A.X during nucleosome assembly in Xenopus laevis oocytes involvement of protein phosphorylation in nucleosome spacing. EMBO J. 10, 3043-3050. 

Protein-protein interactions between the histone subunits are undoubtedly important in promoting formation of a nucleosome in which 146 base pairs of DNA are coiled around the outside of the histone core. One molecule of histone HI binds to an exterior region of each nucleosome, but histone HI is not needed to determine nucleo-some structure. The distance between nucleosomes is approximately 200 base pairs consequently, in electron micrographs, nucleosomes resemble evenly spaced beads on a string of DNA. Neutron and x-ray diffraction data are also consistent with this structure. 

Fig. 1. The core particle, the DNA superhelix and H2B and H3 N-terminal tails, (a) Space-filling representation of the 2.8 A crystal structure of the 146 bp human a-satellite nucleosome core particle [22]. The dyad is in the plane of the paper and the superhelix axis slightly off that plane. Positive and negative numbers mark the superhelix locations (SHL) in the upper and lower gyres, respectively, and the dotted curve follows the path of the double helix axis, (b) Ribbon representation of the DNA superhelix slit along a line parallel to its axis, opened out and laid flat on the paper surface. SHL are also indicated, together with H2B and H3 tails passage points between the gyres. (From Fig. 5 in Ref [29].)...

Fuller, F.B. (1971) The writhing number of a space curve. Proc. Natl. Acad. Sci. USA 68, 815-819. Crick, F.H.C. (1976) Linking numbers and nucleosomes. Proc. Natl. Acad. Sci. USA 73,... 

Mg (but not Na" ") results in a structure that is equivalent to the 30-nm compact fiber in the extent of condensation [49]. Finally, the independent and critical function of core histone N-termini in chromatin condensation was demonstrated by showing that nucleosomal filaments reconstituted from core histones lacking their N-terminal domains are unable to condense into folded structures upon an increase of Mg " ", despite the presence of properly bound histone H5 ([50,51], see also Ref. [52] for the discussion of the special role of H3 and H4 tails). Thus, the presence of HI is not a sine-qua-non condition for salt-induced chromatin folding, which can proceed in Hi s absence and is an intrinsic property of filaments consisting of spaced core particles. A key question is how many of the features of the native 30-nm compact fiber are due to the presence of histone HI From the available data it seems that HI may influence the intrinsic folding pathway of the chromatin filament by stabilizing a single ordered conformation. This property can have much to do with the cooperativity of HI interactions within chromatin but also with the way HI is bound to the nucleosome and with the efifect it exerts on the path of linker DNA. 

Tremethick, D.J. and Drew, H.R. (1993) High mobility group proteins 14 and 17 can space nucleosomes in vitro. J Biol. Chem. 268, 11389-11393. 

Control arrays with evenly spaced nucleosomes are disorganized by SWI/SNF compact dimers within these arrays could not be positively identified... 

From the physics point of view, the system that we deal with here—a semiflexible polyelectrolyte that is packaged by protein complexes regularly spaced along its contour—is of a complexity that still allows the application of analytical and numerical models. For quantitative prediction of chromatin properties from such models, certain physical parameters must be known such as the dimensions of the nucleosomes and DNA, their surface charge, interactions, and mechanical flexibility. Current structural research on chromatin, oligonucleosomes, and DNA has brought us into a position where many such elementary physical parameters are known. Thus, our understanding of the components of the chromatin fiber is now at a level where predictions of physical properties of the fiber are possible and can be experimentally tested. 

FIGURE 10.12 Illustration of regularly spaced nucleosomes consisting of histone protein bound to supercoiled DNA, with DNA links between the histone bound units forming a 30 nm higher-order fiber. 

Fig. 1.41. The influence of the nucleosomes on the positioning of DNA-binding proteins. Example of a control region in which two regulatory DNA elements are separated by 60-90 bp but are brought near each other in 3D space via nucleosome formation. The super-helical arrangement of the DNA in the nucleosome brings the the two DNA elements close together. The DNA element-bound proteins PI and P2 are brought into closer contact with each other in this configuration than in a linear arrangement.

FIGURE 24-26 Nucleosomes. Regularly spaced nucleosomes consist of histone complexes bound to DNA. (a) Schematic illustration and (b) electron micrograph. 

Histone chaperones bind histones and facilitate their proper deposition onto DNA by preventing nonspecific histone-DNA interactions (17). Two major histone chaperones are CAF-1 and NAP-1. CAF-1 localizes to the replication fork by binding PCNA and facilitates the deposition of histones H3 and H4 onto the newly synthesized DNA strands (18,19). Subsequently, NAP-1 facilitates the deposition of histones H2A and H2B to complete the nucleosome (20). Using in vitro nucleosome assembly and nuclease digestion mapping assays, it was shown that the periodic spacing of nucleosomes requires the function of ATP-dependent chromatin remodeling factors, such as the ACF/ISWI complex (16, 21). 

Ito T, et al. Drosophila NAP-1 is a core histone chaperone that functions in ATP-facilitated assembly of regularly spaced nucleosomal arrays. Mol. Cell. Biol. 1996 16 3112-3124. 

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