Evolutionary footprints of nucleosome positions in yeast

Washietl, Stefan; Machné, Rainer; Goldman, Nick

doi:10.1016/j.tig.2008.09.003

Cited by 77 publications

(78 citation statements)

References 27 publications

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“…About 70% of interspecific nucleosome architecture changes in yeast are caused by cis effects as opposed to trans-acting factors (23), which supports our inference of a local histone binding phenotype. At the level of sequence evolution, it has been shown that linker regions in yeast coding sequence are more conserved than regions of higher nucleosome occupancy (24,25), in agreement with a previous analysis of chromosome III promoters (15). More specifically, A:T-loss nucleotide changes are reduced in NDRs compared with high-occupancy regions (26), which is consistent with A:T-rich sequence disfavoring nucleosome formation.…”

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confidence: 87%

Fitness landscape for nucleosome positioning

Weghorn

Lässig

2013

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

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Histone-DNA complexes, so-called nucleosomes, are the building blocks of DNA packaging in eukaryotic cells. The histone-binding affinity of a local DNA segment depends on its elastic properties and determines its accessibility within the nucleus, which plays an important role in the regulation of gene expression. Here, we derive a fitness landscape for intergenic DNA segments in yeast as a function of two molecular phenotypes: their elasticity-dependent histone affinity and their coverage with transcription factor binding sites. This landscape reveals substantial selection against nucleosome formation over a wide range of both phenotypes. We use it as the core component of a quantitative evolutionary model for intergenic DNA segments. This model consistently predicts the observed diversity of histone affinities within wild Saccharomyces paradoxus populations, as well as the affinity divergence between neighboring Saccharomyces species. Our analysis establishes histone binding and transcription factor binding as two separable modes of sequence evolution, each of which is a direct target of natural selection.biophysics | nucleosome-depleted regions | evolution of regulation | quantitative traits | inference of selection T he positional organization of nucleosomes in eukaryotic cells is of key importance for the overall chromatin structure and, thus, for the regulation of gene expression (1-3). Nucleosomes form through binding of a histone octamer to a DNA sequence segment of average length 146 base pairs (bp), which wraps around the protein complex (4). Histone-bound DNA segments are interspersed with unbound "linker" segments. Particularly prominent features of this pattern are so-called nucleosome-depleted regions (NDRs). These are extended troughs in occupancy at least ∼100 bp long, primarily located in intergenic DNA. Changes in nucleosome positioning affect the accessibility of local DNA segments for binding interactions with transcription factors and lead to observable changes of gene expression in yeast (3,5).Explaining two correlated molecular functions-histone binding and transcriptional regulation-in the same sequence segment may be seen as a chicken-and-egg problem (6-9). Is transcription factor binding the primary function, which displaces nucleosomes to sequence segments in which transcription is neutral or deleterious? Or, conversely, does nucleosome positioning constrain transcriptional interactions? Here, we address this problem by a quantitative evolutionary analysis of yeast genomes. We infer a fitness landscape for intergenic sequence segments that measures selection on their regulatory interactions and on local nucleosome formation. We capture these functions by two molecular phenotypes, the regulatory binding site content and the histone binding affinity, which reflect distinct biophysical characteristics of a DNA segment. The fitness landscape resulting from our analysis shows substantial selection acting jointly on transcriptional interactions and on nucleosome formation. Specifically, we fi...

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supporting

confidence: 87%

Fitness landscape for nucleosome positioning

Weghorn

Lässig

2013

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

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“…The DNA changing rapidly in these areas cause that the SVM difficult to capture information of nucleosome"s position. This conclusion coincides with Washietl et al who found the substitution rates of nucleosome-linker DNA lower than nucleosome-DNA [8].…”

Section: A Relevance Between the Predicting Accuracy And The Nucleossupporting

confidence: 92%

Prediction of Nucleosome Positioning Based on Support Vector Machine

Feng¹,

Xiao²,

Lü³

et al. 2013

IJBBB

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Abstract-When we used DNA sequences of Saccharomyces cerevisiae whose nucleosome positioning data have been experimentally determined to train a Support Vector Machine (SVM) to predict the nucleosome formation potential of any given sequence of DNA, we observed that chromatin structure has an impact on the evolution of genomic DNA molecules. We have found, on average, 15% lower predictive accuracy rates in nucleosomal DNA than in linker DNA. This widespread local rates heterogeneity represents an evolutionary footprint of nucleosome positions and reveals that nucleosome organization is a genomic feature conserved over evolutionary timescales. IndexTerms-Evolutionary footprints, nucleosome, predictive accuracy rates, transcriptional start sit (TSS).

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“…As regards the origin of nucleosomal signatures, analyses of the substitution rate of mononucleosomal DNA in related species have suggested that nucleosomal positioning relative to the DNA sequence has remained stable over evolutionary timescales (Washietl et al 2008). This long-term association between histones and DNA makes it possible that nucleosomal signatures could have emerged as a consequence of a different rate of mutation or biased repair along mononucleosomal and linker DNA, due to small differences in the structure of histone octamers; in the bias or accessibility of repair proteins (Washietl et al 2008;Sasaki et al 2009); or in the different impact on the sequence of chromatin remodelers or epigenetic modifications.…”

Section: Wwwgenomeorgmentioning

confidence: 99%

Nucleosomal signatures impose nucleosome positioning in coding and noncoding sequences in the genome

et al. 2016

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In the yeast genome, a large proportion of nucleosomes occupy well-defined and stable positions. While the contribution of chromatin remodelers and DNA binding proteins to maintain this organization is well established, the relevance of the DNA sequence to nucleosome positioning in the genome remains controversial. Through quantitative analysis of nucleosome positioning, we show that sequence changes distort the nucleosomal pattern at the level of individual nucleosomes in three species of Schizosaccharomyces and in Saccharomyces cerevisiae. This effect is equally detected in transcribed and nontranscribed regions, suggesting the existence of sequence elements that contribute to positioning. To identify such elements, we incorporated information from nucleosomal signatures into artificial synthetic DNA molecules and found that they generated regular nucleosomal arrays indistinguishable from those of endogenous sequences. Strikingly, this information is speciesspecific and can be combined with coding information through the use of synonymous codons such that genes from one species can be engineered to adopt the nucleosomal organization of another. These findings open the possibility of designing coding and noncoding DNA molecules capable of directing their own nucleosomal organization.

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Evolutionary footprints of nucleosome positions in yeast

Cited by 77 publications

References 27 publications

Fitness landscape for nucleosome positioning

Fitness landscape for nucleosome positioning

Prediction of Nucleosome Positioning Based on Support Vector Machine

Nucleosomal signatures impose nucleosome positioning in coding and noncoding sequences in the genome

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