The role of DNA sequence in nucleosome breathing

Abstract

Abstract.Roughly 3/4 of human genomes are sequestered by nucleosomes, DNA spools with a protein core, dictating a broad range of biological processes, ranging from gene regulation, recombination, and replication, to chromosome condensation. Nucleosomes are dynamical structures and temporarily expose wrapped DNA through spontaneous unspooling from either end, a process called site exposure or nucleosome breathing. Here we ask how this process is influenced by the mechanical properties of the wrapped DNA, which is known to depend on the underlying base pair sequence. Using a coarse-grained nucleosome model we calculate the accessibility profiles for site exposure. We find that the process is very sensitive to sequence effects, so that evolution could potentially tune the accessibility of nucleosomal DNA and would only need a small number of mutations to do so.

Nucleosomal DNA dynamics mediate Oct4 pioneer factor binding

“…We found significant differences between the dynamics of the 3 nucleosomes, the nucleosome with most TF binding sites showing the largest amplitude of breathing and twisting motions. This is in agreement with previous studies that revealed the more dynamic nature of natural nucleosomes 13,22,28 .…”

“…Despite the lack of full sampling convergence, we observed a good overlap between independent simulations for nucleosome breathing (Fig 3) and we achieved a wider conformational sampling by combining independent simulations of the same species into ensembles. This enabled us to study both breathing and twisting motions in the nucleosomes and to conclude about the sequence dependence of these motions at a level of detail not feasible in coarse grained simulations, which were previously used to study nucleosome dependent dynamics 22,28 . The atomic resolution provides the means to study the determinant modulators of nucleosome dynamics such the motion of histone tails or the role of anchoring histone residues 15 .…”

“…Therefore, questions that require longer and a higher number of simulations can be addressed. As a result, models of sequence-specific nucleosome dynamics, revealing the role of the sequence in nucleosome breathing and unwrapping 22,28 , or protein-mediated remodeling 29 have been established. However, the descriptions obtained from coarse grained simulations is limited because important details regarding the interactions that modulate nucleosome dynamics are missing.…”

Local DNA Sequence Controls Asymmetry of DNA Unwrapping from Nucleosome Core Particles

“…Taken together, the information in these curves provides insight into how this DNA is released from the histone core. The cumulative unwrapping distribution curve (left) reports that mostly wrapped structures are released at the ends (total numbers of basepairs unwrapped less than $40), consistent with breathing modes previously reported (41). For n T values of $40-60, the curve is relatively flat, suggesting that there are few structures in this region.…”

Shortest paths through synonymous genomes

“…[18,31]), translational positioning [6] (see Refs. [3,32,33]), sequencedependent nucleosome breathing [34] (see Refs. [35,36]), and force induced unwrapping [23,37] (see Ref.…”