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.
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http://dx.doi.org/10.1140/epje/i2017-11596-2 | DOI Listing |
J Chem Phys
January 2025
Department of Physics and Astronomy and Center for Quantitative Biology, Rutgers University, Piscataway, New Jersey 08854, USA.
Nucleosomes are fundamental units of chromatin in which a length of genomic DNA is wrapped around a histone octamer spool in a left-handed superhelix. Large-scale nucleosome maps show a wide distribution of DNA wrapping lengths, which in some cases are tens of base pairs (bp) shorter than the 147 bp canonical wrapping length observed in nucleosome crystal structures. Here, we develop a thermodynamic model that assumes a constant free energy cost of unwrapping a nucleosomal bp.
View Article and Find Full Text PDFbioRxiv
November 2024
Department of Chemistry, College of Staten Island, City University of New York, 2800 Victory Blvd., 6S-238, Staten Island, NY 10314.
This study investigates nucleosome dynamics using both all-atom and coarse-grained (CG) molecular dynamics simulations, focusing on the SIRAH force field. Simulations are performed for two nucleosomal DNA sequences-ASP and Widom-601-over six microseconds at physiological salt concentrations. Comparative analysis of structural parameters, such as groove widths and base pair geometries, reveals good agreement between atomistic and CG models, though CG simulations exhibit broader conformational sampling and greater breathing motion of DNA ends.
View Article and Find Full Text PDFJ Mol Biol
August 2024
Department of Physics and Center for NanoScience (CeNS), LMU Munich, Amaliensstrasse 54, 80799 Munich, Germany; Soft Condensed Matter and Biophysics, Department of Physics and Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 1, 3584 CC Utrecht, the Netherlands. Electronic address:
Nucleosomes are the basic compaction unit of chromatin and nucleosome structure and their higher-order assemblies regulate genome accessibility. Many post-translational modifications alter nucleosome dynamics, nucleosome-nucleosome interactions, and ultimately chromatin structure and gene expression. Here, we investigate the role of two post-translational modifications associated with actively transcribed regions, H3K36me3 and H4K5/8/12/16ac, in the contexts of tri-nucleosome arrays that provide a tractable model system for quantitative single-molecule analysis, while enabling us to probe nucleosome-nucleosome interactions.
View Article and Find Full Text PDFJ Biol Chem
June 2024
Department of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. Electronic address:
The copper reductase activity of histone H3 suggests undiscovered characteristics within the protein. Here, we investigated the function of leucine 126 (H3L126), which occupies an axial position relative to the copper binding. Typically found as methionine or leucine in copper-binding proteins, the axial ligand influences the reduction potential of the bound ion, modulating its tendency to accept or yield electrons.
View Article and Find Full Text PDFChemosphere
May 2024
Nord University, Bodø, Norway. Electronic address:
Nanoplastics (NPs) and persistent organic pollutants such as polychlorinated biphenyls (PCBs) are ubiquitous aquatic pollutants. The coexistence of these pollutants in the environment emphasises the need to study their combined toxicity. NPs can cross biological membranes and act as vectors for other pollutants, whereas PCBs are known for their ability to bioaccumulate and biomagnify.
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