Direct measurements of the nucleosome-forming preferences of periodic DNA motifs challenge established models

Takasuka, Taichi E.; Stein, Arnold

doi:10.1093/nar/gkq279

Cited by 16 publications

(14 citation statements)

References 38 publications

(77 reference statements)

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“…These results suggest that CpG dinucleotides are not favored in the nucleosomal DNA segment whose minor groove face the histone octamer, consistent with previous GWAS results which suggest that for well-positioned nucleosomes, (T + A) tracks are preferentially located in the Minor Groove, while the (G + C) tracks are preferentially located in the Major Groove2930313233. This preference is likely to originate from the ability of CpG dinucleotides to induce bending towards the major groove34.…”

Section: Discussionsupporting

confidence: 89%

DNA Methylation Regulated Nucleosome Dynamics

Jimenez-Useche

Tian

et al. 2013

Sci Rep

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A strong correlation between nucleosome positioning and DNA methylation patterns has been reported in literature. However, the mechanistic model accounting for the correlation remains elusive. In this study, we evaluated the effects of specific DNA methylation patterns on modulating nucleosome conformation and stability using FRET and SAXS. CpG dinucleotide repeats at 10 bp intervals were found to play different roles in nucleosome stability dependent on their methylation states and their relative nucleosomal locations. An additional (CpG)5 stretch located in the nucleosomal central dyad does not alter the nucleosome conformation, but significant conformational differences were observed between the unmethylated and methylated nucleosomes. These findings suggest that the correlation between nucleosome positioning and DNA methylation patterns can arise from the variations in nucleosome stability dependent on their sequence and epigenetic content. This knowledge will help to reveal the detailed role of DNA methylation in regulating chromatin packaging and gene transcription.

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Section: Discussionsupporting

confidence: 89%

DNA Methylation Regulated Nucleosome Dynamics

Jimenez-Useche

Tian

et al. 2013

Sci Rep

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“…Sites near the linkers are the first to unwrap and are therefore easily made accessible, while sites buried deeper in the nucleosome are orders of magnitude less likely to be accessible [34]. Not surprisingly, nucleosome positioning has been shown to be dependent on several structural factors including DNA sequence [35][36][37][38][39][40], DNA modifications [41][42][43], and histone modifications [44][45][46][47], although the relative positioning strength of these effects has been challenged [48,49].…”

Section: Introductionmentioning

confidence: 99%

DNA damage may drive nucleosomal reorganization to facilitate damage detection

2014

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One issue in genome maintenance is how DNA repair proteins find lesions at rates that seem to exceed diffusion-limited search rates. We propose a phenomenon where DNA damage induces nucleosomal rearrangements which move lesions to potential rendezvous points in the chromatin structure. These rendezvous points are the dyad and the linker DNA between histones, positions in the chromatin which are more likely to be accessible by repair proteins engaged in a random search. The feasibility of this mechanism is tested by considering the statistical mechanics of DNA containing a single lesion wrapped onto the nucleosome. We consider lesions which make the DNA either more flexible or more rigid by modeling the lesion as either a decrease or an increase in the bending energy. We include this energy in a partition function model of nucleosome breathing. Our results indicate that the steady state for a breathing nucleosome will most likely position the lesion at the dyad or in the linker, depending on the energy of the lesion. A role for DNA binding proteins and chromatin remodelers is suggested based on their ability to alter the mechanical properties of the DNA and DNA-histone binding, respectively. We speculate that these positions around the nucleosome potentially serve as rendezvous points where DNA lesions may be encountered by repair proteins which may be sterically hindered from searching the rest of the nucleosomal DNA. The strength of the repositioning is strongly dependent on the structural details of the DNA lesion and the wrapping and breathing of the nucleosome. A more sophisticated evaluation of this proposed mechanism will require detailed information about breathing dynamics, the structure of partially wrapped nucleosomes, and the structural properties of damaged DNA.

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“…(11) with L replaced by L/N ), relative to a random DNA sequence. In sum, one can see that without interactions the energy variations required for a good positioning seem to be above the ones measured in experiments [11][12][13][14][15]. In Appendix A 2 we discuss positioning of nucleosomes with only hardcore interaction on energy landscape with non-Gaussian distributions and show that the results in this Section do not change qualitatively in this case.…”

Section: B Disordered Energy Landscape With Gaussian Distributionmentioning

confidence: 80%

“…An obvious competitor of sequences preferences for nucleosomes positioning is thermal fluctuations. All measured binding energy differences between different sequences do not exceed a few k B T even for specially designed strongest binders, which do not exist in known genomes [11][12][13][14][15]. This indicates that, at least in equilibrium, entropic forces are expected to play an important role.…”

Section: Introductionmentioning

confidence: 93%

Conditions for positioning of nucleosomes on DNA

Sheinman¹,

Chung²

2015

Phys. Rev. E

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Positioning of nucleosomes along a eukaryotic genome plays an important role in its organization and regulation. There are many different factors affecting the location of nucleosomes. Some can be viewed as preferential binding of a single nucleosome to different locations along the DNA and some as interactions between neighboring nucleosomes. In this study, we analyze positioning of nucleosomes and derive conditions for their good positioning. Using analytic and numerical approaches we find that, if the binding preferences are very weak, an interplay between the interactions and the binding preferences is essential for a good positioning of nucleosomes, especially on correlated energy landscapes. Analyzing the empirical energy landscape, we conclude that good positioning of nucleosomes in vivo is possible only if they strongly interact. In this case, our model, predicting long-length-scale fluctuations of nucleosomes' occupancy along the DNA, accounts well for the empirical observations.

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Direct measurements of the nucleosome-forming preferences of periodic DNA motifs challenge established models

Cited by 16 publications

References 38 publications

DNA Methylation Regulated Nucleosome Dynamics

DNA Methylation Regulated Nucleosome Dynamics

DNA damage may drive nucleosomal reorganization to facilitate damage detection

Conditions for positioning of nucleosomes on DNA

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