There had been an enduring discrepancy between theoretical and observed measurement of the DNA linking number (ΔLk) constrained by nucleosomes. Here the authors provide measurements of the ΔLk constrained by individual nucleosomes in native chromatin that reconcile this discrepancy.
The interplay between chromatin structure and DNA topology is a fundamental, yet elusive, regulator of genome activities. A paradigmatic case is the “linking number paradox” of nucleosomal DNA, which refers to the incongruence between the near two left-handed superhelical turns of DNA around the histone octamer and the DNA linking number difference (∆Lk) stabilized by individual nucleosomes, which has been experimentally estimated to be about -1.0. Here, we analyze the DNA topology of a library of mononucleosomes inserted into small circular minichromosomes to determine the average ∆Lk restrained by individual nucleosomes in vivo. Our results indicate that most nucleosomes stabilize about -1.26 units of ∆Lk. This value balances the twist (∆Tw ≈ + 0.2) and writhe (∆Wr ≈ -1.5) deformations of nucleosomal DNA in terms of the equation ∆Lk = ∆Tw + ∆Wr. Our finding reconciles the existing discrepancy between theoretical and observed measurement of the ΔLk constrained by nucleosomes.
Intracellular nucleosomes constrain a DNA linking number difference of -1.26 that reconciles the Lk paradox
Joana Segura, Ricky S. Joshi, Ofelia Díaz-Ingelmo, Antonio Valdés, Silvia Dyson, Belén Martínez-García and Joaquim Roca*
Nature Communications Sep 28;9(1):3989 (2018)