A novel roll-and-slide mechanism of DNA folding in chromatin: implications for nucleosome positioning

Tolstorukov, M. Y., Colasanti, A. V., McCandlish, D. M., Olson, W. K., Zhurkin, V. B. (2007) A novel roll-and-slide mechanism of DNA folding in chromatin: implications for nucleosome positioning. J Mol Biol, 371 (3). pp. 725-38. ISSN 0022-2836 (Print)0022-2836 (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/17585938
DOI: 10.1016/j.jmb.2007.05.048

Abstract

How eukaryotic genomes encode the folding of DNA into nucleosomes and how this intrinsic organization of chromatin guides biological function are questions of wide interest. The physical basis of nucleosome positioning lies in the sequence-dependent propensity of DNA to adopt the tightly bent configuration imposed by the binding of the histone proteins. Traditionally, only DNA bending and twisting deformations are considered, while the effects of the lateral displacements of adjacent base pairs are neglected. We demonstrate, however, that these displacements have a much more important structural role than ever imagined. Specifically, the lateral Slide deformations observed at sites of local anisotropic bending of DNA define its superhelical trajectory in chromatin. Furthermore, the computed cost of deforming DNA on the nucleosome is sequence-specific: in optimally positioned sequences the most easily deformed base-pair steps (CA:TG and TA) occur at sites of large positive Slide and negative Roll (where the DNA bends into the minor groove). These conclusions rest upon a treatment of DNA that goes beyond the conventional ribbon model, incorporating all essential degrees of freedom of "real" duplexes in the estimation of DNA deformation energies. Indeed, only after lateral Slide displacements are considered are we able to account for the sequence-specific folding of DNA found in nucleosome structures. The close correspondence between the predicted and observed nucleosome locations demonstrates the potential advantage of our "structural" approach in the computer mapping of nucleosome positioning.

Item Type: Paper
Uncontrolled Keywords: Base Pairing Base Sequence DNA/*chemistry/*metabolism Humans Models, Molecular *Nucleic Acid Conformation Nucleosomes/*chemistry/*metabolism Thermodynamics
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > nucleosome
CSHL Authors:
Communities: CSHL labs > McCandlish lab
Depositing User: Matt Covey
Date Deposited: 18 Jan 2017 20:44
Last Modified: 18 Jan 2017 20:44
PMCID: PMC2000845
Related URLs:
URI: http://repository.cshl.edu/id/eprint/34045

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