In Silico Approaches Reveal the Potential for DNA Sequence-dependent Histone Octamer Affinity to Influence Chromatin Structure in Vivo

Fraser, Ross M.; Allan, James; Simmen, Martin W.

doi:10.1016/j.jmb.2006.08.092

Cited by 7 publications

(9 citation statements)

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“…H2A.Z nucleosomes are overrepresented around the TIS, upstream of the STOP codons and in introns. Experiments are coded as follows: the first letter indicates the last or the last two authors (“P” for Pugh [7], [8], “S” for Segal [1], [6], “F” for Friedman [9],“A” for Allan [14], [27], “SL” for Liu and Struhl [2]); the second letter indicates the deep sequencing platform (“R” for Roche/454 and “I” for Illumina/Solexa); “H2A.Z”, “H3” or “H4” stands for the specificity of the antibody used; and the carbon source is indicated by “YPD” for glucose, “EtOH” for ethanol and “Gal” for galactose. “cl” indicates histones cross-linked to the DNA in vivo, “nc” indicates the no cross-linking, both followed by replicate numbers.…”

Section: Resultsmentioning

confidence: 99%

“…The variable strength of DNA-influenced positioning is most visible on the in vitro nucleosome reconstitutions from purified ovine β-lactoglobulin DNA and chicken erythrocyte histones in the absence of histone chaperones and remodeling enzymes [13], [14], [27] (Figure S5). Intrinsic histone-DNA affinities are likely to be responsible for the high summits in these exceptionally high-coverage experiments.…”

Section: Resultsmentioning

confidence: 99%

“…Nucleosomes slide and/or reposition more intensively in vivo in the presence of chaperones and remodeling enzymes than in nonlinked experiments, where histones were not cross-linked to their in vivo loci by formaldehyde. The fuzziest peaks were formed by nucleosomes reconstituted from purified histones and DNA either in yeast [1], [2] or sheep [13], [14], [27]. Intensive eviction and fuzzy remodeling at the centers of transcriptionally active genes indicate Pol II-complex-mediated remodeling.…”

Section: Introductionmentioning

confidence: 99%

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Weakly Positioned Nucleosomes Enhance the Transcriptional Competency of Chromatin

et al. 2010

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BackgroundTranscription is affected by nucleosomal resistance against polymerase passage. In turn, nucleosomal resistance is determined by DNA sequence, histone chaperones and remodeling enzymes. The contributions of these factors are widely debated: one recent title claims “… DNA-encoded nucleosome organization…” while another title states that “histone-DNA interactions are not the major determinant of nucleosome positions.” These opposing conclusions were drawn from similar experiments analyzed by idealized methods. We attempt to resolve this controversy to reveal nucleosomal competency for transcription.Methodology/Principal FindingsTo this end, we analyzed 26 in vivo, nonlinked, and in vitro genome-wide nucleosome maps/replicates by new, rigorous methods. Individual H2A nucleosomes are reconstituted inaccurately by transcription, chaperones and remodeling enzymes. At gene centers, weakly positioned nucleosome arrays facilitate rapid histone eviction and remodeling, easing polymerase passage. Fuzzy positioning is not due to artefacts. At the regional level, transcriptional competency is strongly influenced by intrinsic histone-DNA affinities. This is confirmed by reproducing the high in vivo occupancy of translated regions and the low occupancy of intergenic regions in reconstitutions from purified DNA and histones. Regional level occupancy patterns are protected from invading histones by nucleosome excluding sequences and barrier nucleosomes at gene boundaries and within genes.Conclusions/SignificanceDense arrays of weakly positioned nucleosomes appear to be necessary for transcription. Weak positioning at exons facilitates temporary remodeling, polymerase passage and hence the competency for transcription. At regional levels, the DNA sequence plays a major role in determining these features but positions of individual nucleosomes are typically modified by transcription, chaperones and enzymes. This competency is reduced at intergenic regions by sequence features, barrier nucleosomes, and proteins, preventing accessibility regulation of untargeted genes. This combination of DNA- and protein-influenced positioning regulates DNA accessibility and competence for regulatory protein binding and transcription. Interactive nucleosome displays are offered at http://chromatin.unl.edu/cgi-bin/skyline.cgi.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Weakly Positioned Nucleosomes Enhance the Transcriptional Competency of Chromatin

et al. 2010

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“…But calculating where the nucleosomes will actually be is complicated by competition between nucleosomes, which occupy space and cannot overlap. If one poses the hypothesis that nucle-osomes equilibrate their locations along the DNA — a conjecture that could at best be only approximately true — then this problem reduces to a famous problem in statistical mechanics, namely that of a one-dimensional solution of hard rods in an external potential, and thus can be approximately solved by Monte Carlo methods 105 or exactly solved by numerical integration 106 , recursion 107 or dynamic programming 78,97 (BOX 2). The solution of these equations yields the probability of a nucleosome starting at each basepair, and the probability that each basepair is covered by any of the 147 different nucleosomes that could potentially cover it (as each nucleosome covers 147 bp).…”

Section: Information Coding and Transfer In Cancermentioning

confidence: 99%

What does physics have to do with cancer?

et al. 2011

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Large-scale cancer genomics, proteomics and RNA-sequencing efforts are currently mapping in fine detail the genetic and biochemical alterations that occur in cancer. However, it is becoming clear that it is difficult to integrate and interpret these data and to translate them into treatments. This difficulty is compounded by the recognition that cancer cells evolve, and that initiation, progression and metastasis are influenced by a wide variety of factors. To help tackle this challenge, the US National Cancer Institute Physical Sciences-Oncology Centers initiative is bringing together physicists, cancer biologists, chemists, mathematicians and engineers. How are we beginning to address cancer from the perspective of the physical sciences?

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“…28 Subsequently, we exploited the in vitro nucleosome positioning data sets to simulate nucleosomal organisation and identified histone octamer density (nucleosome repeat length) as a sensitive modulator of chromatin structure. 29 In the current study, we have remapped in vitro nucleosome positioning on the sheep β-lactoglobulin gene using high-throughput sequencing to characterise the DNA sequences recovered in reconstituted nucleosomes. This change in methodology improves the accuracy and resolution of the data and, most importantly, offers a simple and rapid method to characterise specific genomic DNA sequences in terms of nucleosome positioning.…”

Section: Introductionmentioning

confidence: 99%

High-Resolution Mapping of Sequence-Directed Nucleosome Positioning on Genomic DNA

Fraser¹,

Keszenman-Pereyra²,

Simmen³

et al. 2009

Journal of Molecular Biology

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In Silico Approaches Reveal the Potential for DNA Sequence-dependent Histone Octamer Affinity to Influence Chromatin Structure in Vivo

Cited by 7 publications

References 50 publications

Weakly Positioned Nucleosomes Enhance the Transcriptional Competency of Chromatin

Weakly Positioned Nucleosomes Enhance the Transcriptional Competency of Chromatin

What does physics have to do with cancer?

High-Resolution Mapping of Sequence-Directed Nucleosome Positioning on Genomic DNA

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