A Novel Roll-and-Slide Mechanism of DNA Folding in Chromatin: Implications for Nucleosome Positioning

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.

3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures

“…This structural code governs how the double-helical molecule deforms in response to proteins and when and where the genetic information is expressed. For example, the binding of DNA onto the surface of the nucleosome (the protein-DNA assembly that constitutes the basic packaging unit in the nucleus) involves an indirect structural response dependent on the ease of deforming the constituent base-pair steps 1 . Most regulatory proteins and many enzymes, by contrast, recognize specific, sequence-dependent structural features of individual base pairs, making direct contact with DNA atoms unique to their binding sites 2 .…”

The proto-chromatosome: A fundamental subunit of chromatin?

“…22 On the other hand, if the distribution of nucleosomes between the various particle types is non-random, then the occupancies of specific nucleosome positions may be estimated incorrectly. It may be possible to include the proto-chromatosome data in the analysis by using the fact that they mostly represent 7-bp extensions of known positions.…”

Predicting nucleosome positioning in genomes: Physical and bioinformatic approaches

“…In particular, some authors proposed the existence of a sequence code [4][5][6][7][8][9][10][11][12][13][14][15].…”