Statistical distributions of nucleosomes: nonrandom locations by a stochastic mechanism

Kornberg, Roger D.; Stryer, Lubert

doi:10.1093/nar/16.14.6677

Cited by 269 publications

(309 citation statements)

References 48 publications

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“…Binding of a histone octamer will block potential binding sites for other histone octamers. Furthermore, a strongly positioned histone octamer may position other histone octamers, in a process known as statistical positioning (50). Both these (Table S1) effects are taken into account by applying Percus' equation (34)(35)(36)(37) to the energy landscape for nucleosome positioning (Materials and Methods).…”

Section: Resultsmentioning

confidence: 99%

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

Heijden

Vugt

Logie

et al. 2012

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

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Nucleosome positioning dictates eukaryotic DNA compaction and access. To predict nucleosome positions in a statistical mechanics model, we exploited the knowledge that nucleosomes favor DNA sequences with specific periodically occurring dinucleotides. Our model is the first to capture both dyad position within a few base pairs, and free binding energy within 2 kBT, for all the known nucleosome positioning sequences. By applying Percus’s equation to the derived energy landscape, we isolate sequence effects on genome-wide nucleosome occupancy from other factors that may influence nucleosome positioning. For both in vitro and in vivo systems, three parameters suffice to predict nucleosome occupancy with correlation coefficients of respectively 0.74 and 0.66. As predicted, we find the largest deviations in vivo around transcription start sites. This relatively simple algorithm can be used to guide future studies on the influence of DNA sequence on chromatin organization.

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Section: Resultsmentioning

confidence: 99%

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

Heijden

Vugt

Logie

et al. 2012

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

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“…We emphasize that, in vivo, many additional factors beyond genomic DNA sequence may act to bias the positions of nucleosomes (10,24,28,29). The present results serve to define and quantify just those contributions to nucleosome positioning arising from sequence dependences to histone-DNA interactions.…”

Section: Discussionmentioning

confidence: 98%

“…It is possible that, in vivo, certain site-specific DNA binding proteins or other effects will act to influence the positioning of nucleosomes (10,24,28,29). Such influences may be quantified by a coupling free energy, and Eqs.…”

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confidence: 99%

Nucleosome packaging and nucleosome positioning of genomic DNA

Lowary

Widom

1997

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

118

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The goals of this study were to assess the extent to which bulk genomic DNA sequences contribute to their own packaging in nucleosomes and to reveal the relationship between nucleosome packaging and positioning. Using a competitive nucleosome reconstitution assay, we found that at least 95% of bulk DNA sequences have an affinity for histone octamer in nucleosomes that is similar to that of randomly synthesized DNA; they contribute little to their own packaging at the level of individual nucleosomes. An equation was developed that relates the measured free energy to the fractional occupancy of specific nucleosome positions. Evidently, the bulk of eukaryotic genomic DNA is also not evolved or constrained for significant sequence-directed nucleosome positioning at the level of individual nucleosomes. Implications for gene regulation in vivo are discussed.DNA in nucleosomes is tightly bent in comparison to its persistence length, a length scale of DNA stiffness (1). Substantial mechanical work must be done against the bending stiffness to package DNA in nucleosomes; this mechanical work is done at the expense of the favorable free energy of histone-DNA interactions and subtracts from the net thermodynamic stability of the particles. The free energies involved are surprisingly large. Taking the persistence length of DNA to be 50 nm and assuming that DNA in a nucleosome is uniformly bent in a circular trajectory at a radius of curvature of 4.4 nm leads to an estimated free energy cost (1) for bending DNA in a nucleosome of Ϸ75 kcal⅐mol Ϫ1 . Indeed, because of previous estimates such as this, it was once considered remarkable that nucleosome exist at all. Analogous problems exist for DNA twist.The discovery that certain DNA sequences are naturally bent (2) suggested that eukaryotic genomic DNA sequences might be evolved or constrained to facilitate their packaging in nucleosomes (3, 4). Moreover, one might anticipate the existence of a relationship between the free energy of nucleosomal packaging and the phenomenon of nucleosome positioning (such an equation is developed in the present study), suggesting the possibility that nucleosome positioning signals may be encoded in genomic DNA. This idea is interesting in part because of the relationship between nucleosome positioning and gene regulation (5).Results from several studies support the hypothesis that genomes are evolved to facilitate their own packaging. (i) Analyses of DNA fragments present in isolated nucleosome core particles, chromatosomes, and dinucleosomes reveal nonrandom periodic distributions of certain dinucleotides and longer sequences, with particular relative phases (see ref. 6 and references therein). The results suggest that such sequences facilitate the bending of DNA that is necessary for nucleosome formation and that the bending may be produced by an anisotropic flexibility of the AϩT-rich and GϩC-rich regions.(ii) Shrader and Crothers (7, 8) designed sequences de novo that obeyed these rules. The designed sequences were found to bind his...

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“…The shift suggests that as part of the pausing process, Pol II collides with the +1 nucleosome, possibly displacing it downstream by one turn of the DNA helix. If the downstream nucleosomes are positioned in large part by the principles of statistical positioning 40,41 , rather than the underlying DNA sequence, then a shift of the +1 nucleosome is expected to have a ripple effect on downstream nucleosomes.To test the prediction that Pol II is engaging the +1 nucleosome, bulk mononucleosomes were prepared from formaldehyde crosslinked embryos and immunoprecipitated with antibodies directed against Pol II. DNA corresponding to mononucleosomes (~150 bp) was gel-purified and mapped to the entire Drosophila genome with high resolution tiling arrays.…”

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confidence: 99%

Nucleosome organization in the Drosophila genome

Mavrich

Jiang

Ioshikhes

et al. 2008

Nature

662

690

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Comparative genomics of nucleosome positions provides a powerful means for understanding how the organization of chromatin and the transcription machinery co-evolve. Here we produce a high resolution reference map of H2A.Z and bulk nucleosome locations across the genome of the fly D. melanogaster, and compare it to that from the yeast S. cerevisiae. Like Saccharomyces, Drosophila nucleosomes are organized around active transcription start sites in a canonical −1, NFR (nucleosome-free region), +1 arrangement. However, Drosophila does not incorporate H2A.Z into the −1 nucleosome and does not bury its transcriptional start site in the +1 nucleosome. At thousands of genes, RNA polymerase II engages the +1 nucleosome and pauses. How the transcription initiation machinery contends with the +1 nucleosome appears to be fundamentally different between lower and higher eukaryotes.Knowledge of the precise location of nucleosomes in a genome is essential in order to understand the context in which chromosomal processes such as transcription and DNA replication operate. A common theme to emerge from recent genome-wide maps of nucleosome locations is a general deficiency of nucleosomes in promoter regions and an enrichment of certain histone modifications towards the 5′ end of genes [1][2][3][4][5][6][7] . A high resolution genomic map of nucleosome locations in the budding yeast S. cerevisiae has further revealed Correspondence and request for material should be addressed to B.F.P. (bfp2@psu.edu). * These authors contributed equally to this work.Author Information Sequence data deposition is through NCBI Trace Archives TI SRA000283, Sequencing Center = "CCGB", and microarray deposition through ArrayExpress, Accession numbers E-MEXP-1515 and -1519. Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interest.Author Contributions T.M. prepared and purified the nucleosomes including Pol II-bound nucleosomes; C.J. analyzed the nucleosome mapping data and its relationship to other genomic features; I.P.I. performed computational analyses related to nucleosome positioning sequences; X.L. conducted ChIP-chip on Pol II; B.J.V. conducted ChIP-chip on nucleosome-Pol II interactions; S.J.Z. provided bioinformatics support; L.T. constructed libraries and sequenced nucleosomal DNA; J.Q. mapped sequencing reads to the yeast genome; RG provided H2A.Z antibodies; SCS directed the DNA sequencing phase; DSG directed embryo preparations and helped interpret the data; I.A. developed computational approaches to derive nucleosome maps from the read locations and developed the associated browser; B.F.P. directed the project, interpreted the data, and wrote the paper. S6). Those 112,750 nucleosomes detected three or more times were further analyzed, although patterns were identical when all nucleosomes were analyzed. The internal median error of the data was 4 bp (Fig. S7). H2A.Z nucleosomes were predominantly distributed at 175 bp intervals from the TSS (compared to 165 ...

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Statistical distributions of nucleosomes: nonrandom locations by a stochastic mechanism

Cited by 269 publications

References 48 publications

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

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

Nucleosome packaging and nucleosome positioning of genomic DNA

Nucleosome organization in the Drosophila genome

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