The nucleosome hypothesis proposed by Roger Kornberg in 1974 was a paradigm shift for understanding eukaryotic gene expression. The assembly of DNA into chromatin involves a range of events, beginning with the formation of the basic unit, the nucleosome, and ultimately giving rise to a complex organization of specific domains within the nucleus.
The first step is the assembly of the DNA with a newly synthesized tetramer (H3-H4), are specifically modified (e.g. H4 is acetylated at Lys5 and Lysl2 (H3-H4)), to form a subnucleosomal particle, which is followed by the addition of two H2A-H2B dimers. This produces a nucleosomal core particle consisting of 146 base pairs of DNA bind around the histone octamer. This core particle and the linker DNA together form the nucleosome (Figs 4.38 and 4.39).
The next step is the maturation step that requires ATP to establish regular spacing of the nucleosome cores to form the nucleo-filament. During this step the newly incorporated histones are de-acetylated. Next the incorporation of linker histones is accompanied by folding of the nucleo-filament into the 30 nm fibre, the structure of which remains to be elucidated. Two principal models exist- the solenoid model and the zig-zag. Finally, further successive folding events lead to a high level of organization and specific domains in the nucleus.
Two molecules of each of the four core histone proteins form the histone octamer via formation of one tetramer of H3 and H4 and two dimers of H2A and H2B. Each of these entities is held together by a so called hand-shake motif of protein structure, forms a “beads on a string” like structure. H1 is involved with the packing of the “beads on a string” substructures into a high order structure.
H1 is present in half the amount of the other four histones. This is because unlike the other histones, H1 does not make up the nucleosome “bead”. Instead, it sits on top of the structure, keeping in place the DNA that has wrapped around the nucleosome. Specifically, the H1 protein binds to the “linker DNA” (approximately 80 nucleotides in length) region between the histone beads, helping stabilize the zig-zagged 30 nm chromatin fiber. The nucleosome together with histone HI is called a chromatosome. Chromatosomes are held together by the continuous DNA strand, thus forming linker DNA of 30-50 base pairs in length.