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Abstract Eukaryotic genome and methylome encode DNA fragments’ propensity to form nucleosome particles. Although the mechanical properties of DNA possibly orchestrate such encoding, the definite link between ‘omics’ and DNA energetics has remained elusive. Here, we bridge the divide by examining the sequence-dependent energetics of highly bent DNA. Molecular dynamics simulations of 42 intact DNA minicircles reveal that each DNA minicircle undergoes inside-out conformational transitions with the most likely configuration uniquely prescribed by the nucleotide sequence and methylation of DNA. The minicircles’ local geometry consists of straight segments connected by sharp bends compressing the DNA’s inward-facing major groove. Such an uneven distribution of the bending stress favors minimum free energy configurations that avoid stiff base pair sequences at inward-facing major grooves. Analysis of the minicircles’ inside-out free energy landscapes yields a discrete worm-like chain model of bent DNA energetics that accurately account for its nucleotide sequence and methylation. Experimentally measuring the dependence of the DNA looping time on the DNA sequence validates the model. When applied to a nucleosome-like DNA configuration, the model quantitatively reproduces yeast and human genomes’ nucleosome occupancy. Further analyses of the genome-wide chromatin structure data suggest that DNA bending energetics is a fundamental determinant of genome architecture.
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The effect of the kinetoplast edge loop on network percolation
Abstract We use graph theory simulations and single molecule experiments to investigate percolation properties of kinetoplasts, the topologically linked mitochondrial DNA from trypanosome parasites. The edges of some kinetoplast networks contain a fiber of redundantly catenated DNA loops, but previous investigations of kinetoplast topology did not take this into account. Our graph simulations track the size of connected components in lattices as nodes are removed, analogous to the removal of minicircles from kinetoplasts. We find that when the edge loop is taken into account, the largest component after the network de‐percolates is a remnant of the edge loop, before it undergoes a second percolation transition and breaks apart. This implies that stochastically removing minicircles from kinetoplast DNA would isolate large polycatenanes, which is observed in experiments that use photonicking to stochastically destroy kinetoplasts fromCrithidia fasciculata. Our results imply kinetoplasts may be used as a source of linear polycatenanes for future experiments.
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- Award ID(s):
- 2105113
- PAR ID:
- 10442590
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Journal of Polymer Science
- Volume:
- 62
- Issue:
- 7
- ISSN:
- 2642-4150
- Format(s):
- Medium: X Size: p. 1287-1295
- Size(s):
- p. 1287-1295
- Sponsoring Org:
- National Science Foundation
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