The higher order structure of chromatin and histone H1
Authors: Thomas Jean O. 
Published: April 2013

ABSTRACT
The basic chromatin fibre (the 10 nm diameter fibre) is a linear repeating array of nucleosomes, or nucleosome filament. The core of each disk-like nucleosome is a wedge-shaped protein octamer containing two molecules of each of the four core histones (H3, H4, H2A and H2B) around which two turns of DNA are wound in a left-handed superhelix with about 80 base-pairs per turn. The two turns are sealed by a molecule of the fifth histone H1 (or H5 in nucleated erythrocytes). The linker DNA that connects one two-turn particle to the next varies from essentially zero to about 80 base-pairs in chromatins from different sources. The exact significance of this variation is unclear.
Interphase chromatin exists largely in the form of 30 nm fibres. Folding of the nucleosome filament into very similar 30 nm fibres, which is Hl-dependent, occurs in vitro in the presence of monovalent cations or much lower concentrations of divalent cations. These higher-order structures probably arise by helical coiling of the nucleosome filament into a solenoid. Systematic studies of chromatin folding in solution, for a range of chromatin fragment sizes and ionic strengths, reveal two discontinuities in behaviour that reflect two structural transitions. One is interpreted as the formation of a turn of a solenoid with about six nucleosomes, at ionic strength 25 HIM, and is a common feature of chromatin from three different sources, which differ in DNA repeat length, and type and amount of Hl. The other transition is interpreted in terms of hydrodynamic shearing of long solenoids at low ionic strengths (below ∼45mM). It suggests a more stable higher-order structure for chicken erythrocyte chromatin than for rat liver chromatin (attributed largely to the presence of H5), and may prove to be a useful general assay for the relative stabilities of different chromatins, which might be relevant to their ease of unravelling for transcription. A study of short (165 base-pair) repeat chromatin from cerebral cortex neurons has led to the suggestion that in the general case the linker DNA might be located, perhaps with Hl, in the central hole in the solenoid.
H1 molecules in both extended and condensed chromatin (although not when dissociated from it) are close enough to be chemically cross-linked with reagents of span 2-12Å. This suggests an H1 polymer in chromatin, which might have a role in chromatin condensation. Chemical cross-linking studies using cleavable, bifunctional amino-group reagents have permitted the domains of H1 molecules that are in proximity in the extended and condensed states to be determined, and changes occurring on folding to be identified.
In another approach towards understanding the role and behaviour of H1 we have studied further the ability of H1 molecules to migrate between sites on different chromatin fragments. H1 and H5 (an extreme H1 variant) also exchange, but show differences in behaviour that may reflect their different abilities to stabilize higher-order structures, revealed in the sedimentation studies outlined above. In particular, H5 shows a greater preference than H1 for sites in higher-order structures.