Sequence-dependent DNA structure: tetranucleotide conformational maps

Packer, Martin J.; Dauncey, Mark P.; Hunter, Christopher A.

doi:10.1006/jmbi.1999.3237

Cited by 202 publications

(218 citation statements)

References 37 publications

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“…It is significant that the normalized roll angles proposed by Morozov et al [31] are very similar to those achieved by minimizing the conformational energy of the different dinucleotide steps we proposed about 25 years ago [50] and more recently confirmed adopting similar calculations by Packer et al [53]. Fig.…”

Section: Accepted M Manuscriptsupporting

confidence: 84%

Predicting nucleosome positioning in genomes: Physical and bioinformatic approaches

Scipioni

Santis

2011

Biophysical Chemistry

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In eukaryotic genomes, nucleosomes are responsible for packaging DNA and controlling gene expression. For this reason, an increasing interest is arising on computational methods capable of predicting the nucleosome positioning along genomes. In this review we describe and compare bioinformatic and physical approaches adopted to predict nucleosome occupancy along genomes. Computational analyses attempt at decoding the experimental nucleosome maps of genomes in terms of certain dinucleotide step periodicity observed along DNA. Such investigations show that highly significant information about the occurrence of a nucleosome along DNA is intrinsic in certain features of the sequence suggesting that DNA of eukaryotic genomes encodes nucleosome organization. Besides the bioinformatic approaches, physical models were proposed based on the sequence dependent conformational features of the DNA chain, which govern the free energy needed to transform recurrent DNA tracts along the genome into the nucleosomal shape. Graphical abstractHighlights > Theoretical models for predicting nucleosome positioning along genomes are reviewed. > Bioinformatics and physical approaches are compared and discussed. > Mechanical properties of DNA rule thermodynamic stability of nucleosomes. > Nucleosomes are regularly spaced along genomes as required for chromatin fibers. KeywordsThermodynamic stability of nucleosomes; nucleosome code; nucleosome distribution along genomes; bioinformatic approaches for the prediction of nucleosome occupancy; physical models predicting nucleosome occupancy.

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Section: Accepted M Manuscriptsupporting

confidence: 84%

Predicting nucleosome positioning in genomes: Physical and bioinformatic approaches

Scipioni

Santis

2011

Biophysical Chemistry

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“…narrower groove width in A/T regions, intrinsic tendency of CpG and TpG steps to bend into the major groove, 36,38 twist/roll preferences 38 and greater rigidity of ApG and GpA steps compared to CpG and GpC steps 70 ). In fact, it is now accepted that the best residues for DNA recognition can depend on the position of a finger in the protein and/or the effect of neighboring fingers so that each zinc finger is not completely independent.…”

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confidence: 99%

Assessment by Molecular Dynamics Simulations of the Structural Determinants of DNA-binding Specificity for Transcription Factor Sp1

Marco

Garcı́a-Nieto

Gago

2003

Journal of Molecular Biology

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The DNA-binding domain (DBD) of the ubiquituous transcription factor Sp1 consists of three consecutive zinc fingers that recognize a number of nucleotide sequences different from, but related to and sometimes overlapping, those recognized by the structurally better characterized early growth response protein 1 (EGR1, also known as Zif268, Krox-24, and NGFI-A). The accepted consensus binding sequence for Sp1 is usually defined by the asymmetric hexanucleotide core GGGCGG but this sequence does not include, among others, the GAG ( ¼ CTC) repeat that constitutes a high-affinity site for Sp1 binding to the wt1 promoter. Since no 3D structure of the whole DBD of Sp1 is available, either alone or in complex with DNA, a homology-based model was built and its interaction with two DNA 14-mers was studied using nanosecond molecular dynamics simulations in the presence of explicit water molecules. These oligonucleotides represent Sp1 target sites that are present in the promoters of the mdr1 and wt1 genes. For comparative purposes and validation of the protocol, the complex between the DBD of EGR1 and its DNA target site within the proximal mdr1 promoter was simulated under the same conditions. Some water molecules were seen to play an important role in recognition and stabilization of the protein-DNA complexes. Our results, which are supported by the available experimental evidence, suggest that the accuracy in the prediction of putative Sp1-binding sites can be improved by interpreting a set of rules, which are a blend of both stringency and tolerance, for the juxtaposed triplet subsites to which each zinc finger binds. Our approach can be extrapolated to WT1 and other related natural or artificial zinc-finger-containing DNA-binding proteins and may aid in the assignment of particular DNA stretches as allowed or disallowed-binding sites.

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“…Parameter sets exist for predicting DNA curvature based on roll and tilt values for dinucleotide (9)(10)(11)(12)(13) and tetranucleotide (14) steps, but the dinucleotide parameters vary considerably from set to set (15). Nor is there sufficient data to define unambiguously the sequence dependence of the experimental persistence length, except for repeating polymers such as alternating poly[d(A-T)] and poly[d(G-C)], which are found to be relatively more and less flexible, respectively, than genomic DNA (3,16).…”

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confidence: 99%

“…Nor is there sufficient data to define unambiguously the sequence dependence of the experimental persistence length, except for repeating polymers such as alternating poly[d(A-T)] and poly[d(G-C)], which are found to be relatively more and less flexible, respectively, than genomic DNA (3,16). Potentially predictive parameters for roll, tilt, and twist flexibilities of individual base pair steps are available from the standard deviation of these parameters in the crystallographic database (11,12) and accompanying computational approaches (13,14). De Santis and colleagues (17) have shown that bending flexibility parameters based on thermal stability have predictive power for sequence-dependent nucleosome binding affinity.…”

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confidence: 99%

Global structure and mechanical properties of a 10-bp nucleosome positioning motif

Roychoudhury

Sitlani

Lapham

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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The method of DNA cyclization kinetics reveals special properties of the TATAAACGCC sequence motif found in DNA sequences that have high affinity for core histones. Replacement of 30 bp of generic DNA by three 10-bp repeats of the motif in small cyclization constructs increases cyclization rates by two orders of magnitude. We document a 13°bend in the motif and characterize the direction of curvature. The bending force constant is smaller by nearly 2-fold and there is a 35% decrease in the twist modulus, relative to generic DNA. These features are the likely source of the high affinity for bending around core histones to form nucleosomes. Our results establish a protocol for determination of the ensembleaveraged global solution structure and mechanical properties of any Ϸ10-bp DNA sequence element of interest, providing information complementary to that from NMR and crystallographic structural studies.D NA in cells is highly compacted from the unfettered size it would have if free in solution. The first stage of packaging is achieved by wrapping DNA around core histones in a welldefined conformation (1), forming a beads-on-a-string structure that is further compacted by additional proteins into folded chromatin and ultimately into metaphase chromosomes. Interphase chromatin is generally less condensed, but it contains regulatory sites such as promoters at which DNA must be distorted to enable interactions between proteins that bind distant sites on linear DNA. As a relatively stiff polymer, DNA resists the bending required for packaging, which requires free energy assistance from strong interactions with core histones and other proteins.Variations in DNA sequence can, in principle, modulate the energy cost of bending and packaging. For example, intrinsic curvature of the kind provided by A-tracts (2) should, if in the proper direction, lessen the energy required for bending. Increased local bending flexibility could reduce the energetic cost of packaging, as could an increase in twist flexibility (3), assuming that the helical phasing between distal regulatory sequence elements must be altered to form a protein complex.The stiffness of DNA (the inverse of its flexibility) is traditionally described by the persistence length P, defined as the average projection of the end-to-end vector of a very long chain on its initial direction. Classical techniques, such as light scattering (4) and rotational diffusion (5), supplemented by DNA cyclization kinetics (6), have led to estimates of around 140-180 bp for P. However, these methods are generally unable to deconvolute rigorously the contributions of curvature and flexibility to apparent persistence length (7), unless special constructs are used (8).Parameter sets exist for predicting DNA curvature based on roll and tilt values for dinucleotide (9-13) and tetranucleotide (14) steps, but the dinucleotide parameters vary considerably from set to set (15). Nor is there sufficient data to define unambiguously the sequence dependence of the experimental persistence length, ...

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Sequence-dependent DNA structure: tetranucleotide conformational maps

Cited by 202 publications

References 37 publications

Predicting nucleosome positioning in genomes: Physical and bioinformatic approaches

Predicting nucleosome positioning in genomes: Physical and bioinformatic approaches

Assessment by Molecular Dynamics Simulations of the Structural Determinants of DNA-binding Specificity for Transcription Factor Sp1

Global structure and mechanical properties of a 10-bp nucleosome positioning motif

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