Dataset Information

Modeling DNA-bending in the nucleosome: role of AA periodicity.

ABSTRACT: This paper uses atomistic molecular mechanics within the framework of the JUMNA model to study the bending properties of DNA segments, with emphasis on understanding the role of the 10 bp periodicity associated with AA repeats that has been found to dominate in nucleosomal DNA. The calculations impose a bending potential on 18 bp segments that is consistent with nucleosome structures (i.e., radius of curvature of 4.1 nm), and then determine the energies of the minimum energy structures for different values of the rotational register (a measure of the direction of bending of the DNA) subject to forces derived from the Amber force field (parm99bsc0). The results show that sequences that contain the 10 bp repeats but are otherwise random have a narrow distribution of rotational register values that minimize the energy such that it is possible to combine several minimized structures to give the 147 bp nearly planar loop structure of the nucleosome. The rotational register values that lead to minimum bending energy with 10 bp AA repeats have a narrower minor groove, which points toward the histone interior at the positions of the AA repeats, which is a result that matches the experiments. The calculations also show that these sequences have a relatively flat potential energy landscape for bending to a 4.1 nm radius of curvature. Random sequences that do not have the 10 bp AA repeats have less stable bent structures, and a flat rotational register distribution, such that low energy nearly planar loops are less likely.

SUBMITTER: Prytkova TR

PROVIDER: S-EPMC3140867 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Modeling DNA-bending in the nucleosome: role of AA periodicity.

Prytkova Tatiana R TR Zhu Xiao X Widom Jonathan J Schatz George C GC

The journal of physical chemistry. B 20110616 26

This paper uses atomistic molecular mechanics within the framework of the JUMNA model to study the bending properties of DNA segments, with emphasis on understanding the role of the 10 bp periodicity associated with AA repeats that has been found to dominate in nucleosomal DNA. The calculations impose a bending potential on 18 bp segments that is consistent with nucleosome structures (i.e., radius of curvature of 4.1 nm), and then determine the energies of the minimum energy structures for diffe ...[more]

PMID: 21639136

Similar Datasets

Project description:Nucleosomes form the fundamental building blocks of chromatin. Subtle modifications of the constituent histone tails mediate chromatin stability and regulate gene expression. For this reason, it is important to understand structural dynamics of nucleosomes at atomic levels. We report a novel multiscale model of the fundamental chromatin unit, a nucleosome, using a simplified model for rapid discrete molecular dynamics simulations and an all-atom model for detailed structural investigation. Using a simplified structural model, we perform equilibrium simulations of a single nucleosome at various temperatures. We further reconstruct all-atom nucleosome structures from simulation trajectories. We find that histone tails bind to nucleosomal DNA via strong salt-bridge interactions over a wide range of temperatures, suggesting a mechanism of chromatin structural organization whereby histone tails regulate inter- and intranucleosomal assemblies via binding with nucleosomal DNA. We identify specific regions of the histone core H2A/H2B-H4/H3-H3/H4-H2B/H2A, termed "cold sites", which retain a significant fraction of contacts with adjoining residues throughout the simulation, indicating their functional role in nucleosome organization. Cold sites are clustered around H3-H3, H2A-H4 and H4-H2A interhistone interfaces, indicating the necessity of these contacts for nucleosome stability. Essential dynamics analysis of simulation trajectories shows that bending across the H3-H3 is a prominent mode of intranucleosomal dynamics. We postulate that effects of salts on mononucleosomes can be modeled in discrete molecular dynamics by modulating histone-DNA interaction potentials. Local fluctuations in nucleosomal DNA vary significantly along the DNA sequence, suggesting that only a fraction of histone-DNA contacts make strong interactions dominating mononucleosomal dynamics. Our findings suggest that histone tails have a direct functional role in stabilizing higher-order chromatin structure, mediated by salt-bridge interactions with adjacent DNA.

Project description:The protein-coding regions (coding exons) of a DNA sequence exhibit a triplet periodicity (TP) due to fact that coding exons contain a series of three nucleotide codons that encode specific amino acid residues. Such periodicity is usually not observed in introns and intergenic regions. If a DNA sequence is divided into small segments and a Fourier Transform is applied on each segment, a strong peak at frequency 1/3 is typically observed in the Fourier spectrum of coding segments, but not in non-coding regions. This property has been used in identifying the locations of protein-coding genes in unannotated sequence. The method is fast and requires no training. However, the need to compute the Fourier Transform across a segment (window) of arbitrary size affects the accuracy with which one can localize TP boundaries. Here, we report a technique that provides higher-resolution identification of these boundaries, and use the technique to explore the biological correlates of TP regions in the genome of the model organism C. elegans.Using both simulated TP signals and the real C. elegans sequence F56F11 as an example, we demonstrate that, (1) Modified Wavelet Transform (MWT) can better define the boundary of TP region than the conventional Short Time Fourier Transform (STFT); (2) The scale parameter (a) of MWT determines the precision of TP boundary localization: bigger values of a give sharper TP boundaries but result in a lower signal to noise ratio; (3) RNA splicing sites have weaker TP signals than coding region; (4) TP signals in coding region can be destroyed or recovered by frame-shift mutations; (5) 6 bp periodicities in introns and intergenic region can generate false positive signals and it can be removed with 6 bp MWT.MWT can provide more precise TP boundaries than STFT and the boundaries can be further refined by bigger scale MWT. Subtraction of 6 bp periodicity signals reduces the number of false positives. Experimentally-introduced frame-shift mutations help recover TP signal that have been lost by possible ancient frame-shifts. More importantly, TP signal has the potential to be used to detect the splice junctions in fully spliced mRNA sequence.

Dataset Information

Modeling DNA-bending in the nucleosome: role of AA periodicity.

Publications

Modeling DNA-bending in the nucleosome: role of AA periodicity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets