Eukaryotic cells condense their genetic material in the nucleus in the form of chromatin, a macromolecular complex made of DNA and multiple proteins. The structure of chromatin is intimately connected to the regulation of all eukaryotic organisms, from amoebas to humans, but its organization remains largely unknown. The nucleosome repeat length (NRL) and the concentration of linker histones (ρLH) are two structural parameters that vary among cell types and cell cycles; the NRL is the number of DNA basepairs wound around each nucleosome core plus the number of basepairs linking successive nucleosomes. Recent studies have found a linear empirical relationship between the variation of these two properties for different cells, but its underlying mechanism remains elusive. Here we apply our established mesoscale chromatin model to explore the mechanisms responsible for this relationship, by investigating chromatin fibers as a function of NRL and ρLH combinations. We find that a threshold of linker histone concentration triggers the compaction of chromatin into well-formed 30-nm fibers; this critical value increases linearly with NRL, except for long NRLs, where the fibers remain disorganized. Remarkably, the interaction patterns between core histone tails and chromatin elements are highly sensitive to the NRL and ρLH combination, suggesting a molecular mechanism that could have a key role in regulating the structural state of the fibers in the cell. An estimate of the minimized work and volume associated with storage of chromatin fibers in the nucleus further suggests factors that could spontaneously regulate the NRL as a function of linker histone concentration. Both the tail interaction map and DNA packing considerations support the empirical NRL/ρLH relationship and offer a framework to interpret experiments for different chromatin conditions in the cell.
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