On the Relationship between DNA Periodicity and Local Chromatin Structure

Reynolds, Sheila M.; Bilmes, Jeff; Noble, William Stafford

doi:10.1007/978-3-642-02008-7_31

Cited by 4 publications

(5 citation statements)

References 36 publications

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“…By contrast, both DAC and DCC functions in mouse and human genes exhibit no recognizable peaks and SS patterns are missing in mammals, consistent with earlier studies (Tolstorukov et al 2009;Reynolds et al 2009). This lack of sequence periodicity in mammals is remarkable because it suggests that the enrichment of anti-WW/SS nucleosomes is not due to intrinsic DNA sequence patterns but to trans-acting factors such as RNA Pol II.…”

Section: Periodic Dna Patterns Are Missing In Mammalian Genessupporting

confidence: 90%

An unusual nucleosomal sequence pattern is enriched in mammalian genes

2017

Preprint

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The rotational positioning of nucleosomes is associated with certain periodic DNA patterns, with the well-known preference of WW dinucleotides (where W is A or T) and SS dinucleotides (where S is G or C) to occur at the sites where nucleosomeal DNA bends into the minor and major grooves, respectively.However, cis-and trans-acting factors governing this nucleosome positioning sequence (NPS) pattern remain unclear. To identify these factors, we performed a systematic analysis of WW/SS patterns within 147-bp nucleosome core particle fragments in different eukaryotes under multiple cellular conditions. We find that >50% of nucleosomes in the genomes do not have this NPS pattern and >20% of nucleosomes take the inverse, anti-NPS pattern. The fraction of anti-NPS nucleosomes is increased in cells lacking one or more chromatin remodelers and in genes with high RNA polymerase II (Pol II) transcription frequencies. Remarkably, anti-NPS nucleosomes exhibit distinctive distributions across the yeast and human genomes: the nucleosomes are distributed uniformly in yeast, while in humans they are more enriched at promoters and coding regions than at repetitive DNA elements. Such differences can be explained by intrinsic DNA sequence patterns. Thus, our results suggest that the rotational positioning of nucleosomes can be influenced, in a synergic manner, by cis and trans determinants including DNA sequence, ATP-dependent nucleosome remodeling enzymes and RNA Pol II.peer-reviewed)

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Section: Periodic Dna Patterns Are Missing In Mammalian Genessupporting

confidence: 90%

An unusual nucleosomal sequence pattern is enriched in mammalian genes

2017

Preprint

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“…First, the NPS software uses a bin size of 10 nucleotides in processing the short-read sequencing data and estimating the dyad positions, resulting in an average error of at least 5 nucleotides in each position estimate which would smooth out any 10 bp periodicity in the average pattern. Second, 10 bp periodicity of the AA dinucleotide has to date been observed only in small sets of H. sapiens nucleosomal sequences and is not observable on a genome-wide scale in H. sapiens , in sharp contrast to S. cerevisiae [12], [27]. While removing the binning step in the NPS process may yield more accurate dyad positions, we caution that it may also amplify the impact of the MNase sequence specificity as is apparent in the higher-resolution yeast data set discussed below.…”

Section: Resultsmentioning

confidence: 97%

“…A commonly cited nucleosome affinity feature is a 10 bp periodicity of certain dinucleotides, which was first described by Trifonov et al in 1980 [5] and has since been confirmed in both synthetic [6], [7] and natural sequences from a variety of organisms including chicken [8], mouse [7], S. cerevisiae [4], [9], [10], worm [10], [11], and H. sapiens [12]. The periodic repetition of these sequence elements, with a period that matches the pitch of the DNA helix, is thought to encourage the large-scale bending of the DNA molecule necessary to form a nucleosome.…”

Section: Introductionmentioning

confidence: 91%

Learning a Weighted Sequence Model of the Nucleosome Core and Linker Yields More Accurate Predictions in Saccharomyces cerevisiae and Homo sapiens

2010

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DNA in eukaryotes is packaged into a chromatin complex, the most basic element of which is the nucleosome. The precise positioning of the nucleosome cores allows for selective access to the DNA, and the mechanisms that control this positioning are important pieces of the gene expression puzzle. We describe a large-scale nucleosome pattern that jointly characterizes the nucleosome core and the adjacent linkers and is predominantly characterized by long-range oscillations in the mono, di- and tri-nucleotide content of the DNA sequence, and we show that this pattern can be used to predict nucleosome positions in both Homo sapiens and Saccharomyces cerevisiae more accurately than previously published methods. Surprisingly, in both H. sapiens and S. cerevisiae, the most informative individual features are the mono-nucleotide patterns, although the inclusion of di- and tri-nucleotide features results in improved performance. Our approach combines a much longer pattern than has been previously used to predict nucleosome positioning from sequence—301 base pairs, centered at the position to be scored—with a novel discriminative classification approach that selectively weights the contributions from each of the input features. The resulting scores are relatively insensitive to local AT-content and can be used to accurately discriminate putative dyad positions from adjacent linker regions without requiring an additional dynamic programming step and without the attendant edge effects and assumptions about linker length modeling and overall nucleosome density. Our approach produces the best dyad-linker classification results published to date in H. sapiens, and outperforms two recently published models on a large set of S. cerevisiae nucleosome positions. Our results suggest that in both genomes, a comparable and relatively small fraction of nucleosomes are well-positioned and that these positions are predictable based on sequence alone. We believe that the bulk of the remaining nucleosomes follow a statistical positioning model.

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“…Together, the fact that a periodic signal in the region following the TSS can only be measured using either sensitive autocorrelation measures on individual sequences [ 24 ] or the average dinucleotide frequencies of a large set of sequences (this study) suggests that, in contrast to yeast, the RR/YY dinucleotides in human show only a weak periodicity at the level of individual sequences. We thus resolved to use large sets of sequences by partitioning the TSSs into classes according to properties conventionally used to describe genes and to examine if the signal concentrates in a subset of promoters.…”

Section: Resultsmentioning

confidence: 95%

“…This lack of significant periodic dinucleotide patterns in individual human H2A.Z sequences has been noted previously using autocorrelation analysis, in contrast to yeast nucleosomal sequences, where periodic patterns appear readily [ 8 ] using these approaches. However, a more sensitive autocorrelation analysis, called autocorrelation spectral estimation, recently showed that 10- and 11-bp periodic AA/TT dinucleotide signals exist in human nucleosomal sequences, while the 11-bp signal is specific to the regions flanking the TSS [ 24 ].…”

Section: Resultsmentioning

confidence: 99%