Topological diversity of chromatin fibers: Interplay between nucleosome repeat length, DNA linking number and the level of transcription

Abstract

The spatial organization of nucleosomes in 30-nm fibers remains unknown in detail. To tackle this problem, we analyzed all stereochemically possible configurations of two-start chromatin fibers with DNA linkers L = 10–70 bp (nucleosome repeat length NRL = 157–217 bp). In our model, the energy of a fiber is a sum of the elastic energy of the linker DNA, steric repulsion, electrostatics, and the H4 tail-acidic patch interaction between two stacked nucleosomes. We found two families of energetically feasible conformations of the fibers—one observed earlier, and the other novel. The fibers from the two families are characterized by different DNA linking numbers—that is, they are topologically different. Remarkably, the optimal geometry of a fiber and its topology depend on the linker length: the fibers with linkers L = 10n and 10n + 5 bp have DNA linking numbers per nucleosome ΔLk ≈ −1.5 and −1.0, respectively. In other words, the level of DNA supercoiling is directly related to the length of the inter-nucleosome linker in the chromatin fiber (and therefore, to NRL). We hypothesize that this topological polymorphism of chromatin fibers may play a role in the process of transcription, which is known to generate different levels of DNA supercoiling upstream and downstream from RNA polymerase. A genome-wide analysis of the NRL distribution in active and silent yeast genes yielded results consistent with this assumption.

Precise genome-wide mapping of single nucleosomes and linkers in vivo

“…Our data indicate that even individual genes of the same organism may have a wide range of different NRLs among a population of cells. This suggests that in different cells the same gene may have different chromatin conformations, depending on the corresponding linker lengths [ 92 , 93 ].…”

DNA topology in chromatin is defined by nucleosome spacing

“…Thus, we see that, in the three NAs belonging to the {10 n } series, 12x167, 12x188, and 12x207, the absolute value of DNA linking number, |Δ Lk |, gradually decreases from 1.4 to 1.1 with increase in the linker length, in a good agreement with our predictions based on energy minimization of the fiber topoisomers (fig. S9) ( 45 ).…”

“…The increased fiber “plasticity” observed for the {10 n + 5} linkers ( 43 – 45 ) is biologically relevant because the {10 n + 5} values are frequently found in vivo ( 39 – 43 ). On the other hand, the more tightly folded {10 n } structures appear to facilitate nucleosome disk stacking by interactions between histone H4 N-terminal domain and histone H2A/H2B acidic patch at the nucleosomal interface ( 35 ) and make the structure to be especially sensitive to the effects of histone H4 acetylation ( 52 ).…”

“…Furthermore, using computer modeling, we predicted the two families of energetically stable conformations of the two-start zigzag fibers, one with L = 10 n and the other with L = 10 n + 5 to be topologically different, the former imposing ~50% higher absolute |Δ Lk | values in the circular DNA (see Fig. 1 ) ( 44 , 45 ). Here, we experimentally addressed these predictions for circular nucleosome arrays containing regularly spaced repeats of the 601 nucleosome positioning sequence ( 34 ).…”

Kilobase Pair Chromatin Fiber Contacts Promoted by Living-System-Like DNA Linker Length Distributions and Nucleosome Depletion

“…21 It was later suggested by modeling that this trend is related to the periodicity of the DNA double helix, where DNA topology plays structural roles in the stability of the fiber. 26,27 …”