Figure 4. Transitioning through the thermodynamic landscape of nucleosome assembly.

Histones must transition through a number of protein complexes in order to fold with DNA into nucleosomes without the input of energy from ATP hydrolysis. Immediately after synthesis histones contain a high free energy. This energy may be captured by histone chaperones and utilised in a way which drives correct folding and oligomerisation of histone subunits. This is mostly likely achieved through extensive and specific interactions covering all transitions states of histone intermediates. In such a scenario, accepting potential ATP-driven input from canonical protein folding chaperones in the initial stages, the histone chaperoning pathway may represent an efficient way to assemble a highly abundant cellular complex.