Sequence-based prediction of single nucleosome positioning and genome-wide nucleosome occupancy

Heijden, Thijn van der; Vugt, Joke J.F.A. van; Logie, Colin; Noort, John van

doi:10.1073/pnas.1205659109

Cited by 72 publications

(88 citation statements)

References 77 publications

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“…Third, to test the involvement of nucleosome positioning signals, we used a recent model for prediction of nucleosome positions from DNA sequence (van der Heijden et al 2012). We observed a significantly higher predicted positioning signal in H3K27me3 domains compared with random genomic sequence (Fig.…”

Section: Comparative Analysis Of Sequence Features Of Vertebrate H3k2mentioning

confidence: 99%

Principles of nucleation of H3K27 methylation during embryonic development

et al. 2013

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During embryonic development, maintenance of cell identity and lineage commitment requires the Polycomb-group PRC2 complex, which catalyzes histone H3 lysine 27 trimethylation (H3K27me3). However, the developmental origins of this regulation are unknown. Here we show that H3K27me3 enrichment increases from blastula stages onward in embryos of the Western clawed frog (Xenopus tropicalis) within constrained domains strictly defined by sequence. Strikingly, although PRC2 also binds widely to active enhancers, H3K27me3 is only deposited at a small subset of these sites. Using a Support Vector Machine algorithm, these sequences can be predicted accurately on the basis of DNA sequence alone, with a sequence signature conserved between humans, frogs, and fish. These regions correspond to the subset of blastula-stage DNA methylation-free domains that are depleted for activating promoter motifs, and enriched for motifs of developmental factors. These results imply a genetic-default model in which a preexisting absence of DNA methylation is the major determinant of H3K27 methylation when not opposed by transcriptional activation. The sequence and motif signatures reveal the hierarchical and genetically inheritable features of epigenetic cross-talk that impose constraints on Polycomb regulation and guide H3K27 methylation during the exit of pluripotency.

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Section: Comparative Analysis Of Sequence Features Of Vertebrate H3k2mentioning

confidence: 99%

Principles of nucleation of H3K27 methylation during embryonic development

et al. 2013

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“…We tested the ability of our computational protocol to predict single nucleosome positions on established target-positioning sequences taken from ref. 13. Fig.…”

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confidence: 99%

“…Although sequence based methods (11)(12)(13)(14)(15) are predictive and cost-effective, they cannot directly account for any structural information, which is especially relevant if one is to distinguish identical sequence motifs with distinct epigenetic marks. Furthermore, current structure-based methods (17)(18)(19)(20) either rely on statistical data from prior experiments (17,18) and lack the information needed to capture epigenetic changes (e.g., methylation) or use fragments (19,20) so that the physical system is not modeled as a whole.…”

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confidence: 99%

“…The pioneering dinucleotide study of Trifonov and Sussman (11) was followed by the first comprehensive study of k-mers, sequence motifs k nucleotides in length (12). In fact, the guiding-dinucleotide model, which accounts for both periodicity and positional dependence, currently predicts single nucleosome positions most accurately (13). Other powerful knowledge-based approaches for predicting nucleosome organization (14) and single-nucleosome positioning (15) were developed using global and position-dependent preferences for k-mer sequences (14,15).…”

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confidence: 99%

“…As such it can be applied to methylated DNA, for which statistical data are difficult to obtain. Therefore, our method can provide this missing link, the occupancy profile for modified DNA, on which knowledge-based methods (13,14) can then be trained and used to study the genome-wide effect of DNA based epigenetics on nucleosome occupancy.…”

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Training-free atomistic prediction of nucleosome occupancy

Mináry

Levitt

2014

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

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Nucleosomes alter gene expression by preventing transcription factors from occupying binding sites along DNA. DNA methylation can affect nucleosome positioning and so alter gene expression epigenetically (without changing DNA sequence). Conventional methods to predict nucleosome occupancy are trained on observed DNA sequence patterns or known DNA oligonucleotide structures. They are statistical and lack the physics needed to predict subtle epigenetic changes due to DNA methylation. The training-free method presented here uses physical principles and state-of-the-art all-atom force fields to predict both nucleosome occupancy along genomic sequences as well as binding to known positioning sequences. Our method calculates the energy of both nucleosomal and linear DNA of the given sequence. Based on the DNA deformation energy, we accurately predict the in vitro occupancy profile observed experimentally for a 20,000-bp genomic region as well as the experimental locations of nucleosomes along 13 well-established positioning sequence elements. DNA with all C bases methylated at the 5 position shows less variation of nucleosome binding: Strong binding is weakened and weak binding is strengthened compared with normal DNA. Methylation also alters the preference of nucleosomes for some positioning sequences but not others.transcriptional regulation | sequence threading | large-scale optimization I n cells, DNA molecules are stored in the form of chromatin that consists of repeating nucleosome units with superhelical DNA wrapped around a protein octamer core (1, 2). Neighboring nucleosomes are connected by extended straight stretches of DNA called the linker region. Given that certain transcription factors prefer to bind to naked DNA (3), a bound nucleosome may silence the genetic message of its DNA segment. Although the in vitro nucleosome occupancy is mainly governed by physical principles setting preferences for certain sequences, the exact placement of nucleosomes in vivo will also be influenced by higher order chromatin structure (3), chromatin remodeling (4), interaction with DNA-binding transcription factors (5), and epigenetic factors (6) such as histone modifications and DNA methylation (7). These subtle epigenetic changes (often referred to as chromatin marks) may provide a convenient way to manipulate genetic expression without altering the underlying genetic code. As a result, they have become a central focus of modern biomedical research. Here, we present a structurebased, in silico approach that captures how a DNA-based epigenetic mark, methylation, affects both the distribution of nucleosomes along genomic sequences and their preferred dyad location along known nucleosome-positioning sequences. The present work constitutes, to our knowledge, the first step toward computational structural epigenetics.This central importance in transcriptional regulation inspired development of experimental methods to map nucleosome positions. The most commonly used approach employs micrococcal nuclease to cleave DNA along the ...

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A deformation energy model reveals sequence-dependent property of nucleosome positioning

et al. 2021

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We present a deformation energy model for predicting nucleosome positioning, in which a position-dependent structural parameter set derived from crystal structures of nucleosomes was used to calculate the DNA deformation energy. The model is successful in predicting nucleosome occupancy genome-wide in budding yeast, nucleosome free energy, and rotational positioning of nucleosomes. Our model also indicates that the genomic regions underlying the MNase-sensitive nucleosomes in budding yeast have high deformation energy and, consequently, low nucleosome-forming ability, while the MNase-sensitive non-histone particles are characterized by much lower DNA deformation energy and high nucleosome preference. In addition, we also revealed that remodelers, SNF2 and RSC8, are likely to act in chromatin remodeling by binding to broad nucleosome-depleted regions that are intrinsically favorable for nucleosome positioning. Our data support the important role of position-dependent physical properties of DNA in nucleosome positioning.

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Sequence-based prediction of single nucleosome positioning and genome-wide nucleosome occupancy

Cited by 72 publications

References 77 publications

Principles of nucleation of H3K27 methylation during embryonic development

Principles of nucleation of H3K27 methylation during embryonic development

Training-free atomistic prediction of nucleosome occupancy

A deformation energy model reveals sequence-dependent property of nucleosome positioning

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