In addition to the genetic message, DNA base sequence carries a multitude of structural and energetic signals important to its biological packaging and function. The statistical mechanical treatment of chain molecules pioneered by Flory provides the foundation behind methods now used to connect information embedded in the DNA base pairs with macromolecular features of the double helix. In contrast to the original treatment of polymers in terms of their chemical backbones, DNA is described in terms of the orientation and displacement of its base-pair side groups. The approach thus takes account of cross-sections as well as connections of residues along the chain. Subtleties in the disposition of base pairs become particularly significant at long chain lengths when proteins attach to widely spaced sites along the DNA and force the intervening residues into loops. The arrangements of base pairs dictate how the DNA folds and whether the ends of the loops lie in correct register with the binding sites on protein. The Flory-based approach is also useful in interpreting the properties of DNA decorated by nucleosomes — the assemblies of DNA and protein that constitute the fundamental packaging unit of chromatin. The number, spacing, and composition of nucleosomes influence the long-range communication between DNA elements involved in the transcription of genes, forming loops orders of magnitude longer than those adopted by bare DNA. The patterns of nucleosome association found to account for properties of model oligonucleosomes can be used to study even longer fragments of DNA. A nucleosome-level depiction of chromatin reduces the complexity of the system along the same lines as a base-pair-level depiction of DNA. The spacing of nucleosomes affects the statistical properties of long chromatin constructs, with polymers of the same length and nucleosome composition exhibiting behaviors dependent upon the number of base pairs between of successive nucleosomes.

Insights into DNA and chromatin from realistic treatment of the double helix

2019 Fall National Meeting

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