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.Graphical abstract
Highlights
Eukaryotic DNA is highly compacted within chromatin to fit inside the nucleus of the cell
A nucleosome consists of 147 base pairs of DNA wrapped around a protein cylinder composed of eight histone proteins
The DNA is represented by the rigid bp model (RBP) [59] which treats each bp as a rigid plate, the spatial position and orientation of which are described by six degrees of freedom
Summary
Eukaryotic DNA is highly compacted within chromatin to fit inside the nucleus of the cell. DNA-protein complex but rather a whole class of complexes, with significant variation in their physical properties This idea has mainly been studied in the context of the sequence-dependent affinity of DNA to the histone octamer, which contributes to the positioning of nucleosomes along genomes (alongside other effects, such as competition for DNA binding with other proteins, and the active positioning by chromatin remodelers [4]). This is sometimes referred to as the “nucleosome positioning code” [5]
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