Determinants of nucleosome organization in primary human cells

Valouev, Anton; Johnson, Steven; Boyd, Scott D.; Smith, C. Lavett; Fire, Andrew; Sidow, Arend

doi:10.1038/nature10002

Cited by 612 publications

(915 citation statements)

References 34 publications

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“…Unlike in experiments that look at nucleosome depletion or retention, the excluded volume between nucleosomes puts a limit on how strong the enrichment can be in practice. This is the reason for the discrepancy between the in vitro results of Valouev et al (34) and ours and those of Vavouri and Lehner (36). To approximate the effects of steric interactions, we applied Percus' equation (42) to our average energy landscapes, and solved it as described in Vanderlick et al (43).…”

Section: Resultsmentioning

confidence: 96%

“…The in vitro nucleosome map produced by Kaplan et al (18) was retrieved from GEO accession number GEO: GSE13622. The map from Valouev et al (34) was downloaded from ccg.vital-it.ch/mga/hg18/valouev11/valouev11.html. The map from Locke et al (38) was downloaded from http://nucleosome.rutgers.edu/ nucenergen/celegansnuc/.…”

Section: Data Acquisitionmentioning

confidence: 99%

“…Instead, it was found that promoter regions in the human genome showed enhanced nucleosome occupancy. One interpretation is that this reflects the differentiated nature of human cells: it may be more beneficial to keep genes relatively inaccessible by default, and to actively open the promoter region only when needed (33,34). This idea seems to be countered by newer results, however, which find stronger intrinsic nucleosome-attracting regions (NARs) for housekeeping genes than for tissue-specific genes, directly opposite of what one would expect (36).…”

Section: Introductionmentioning

confidence: 99%

“…Since the earliest studies on baker's yeast, inquiries into nucleosome positioning have been extended to the genomes of many other organisms, such as Schizosaccharomyces pombe (21) and various other species of yeast (22), Caenorhabditis elegans (23,24), Plasmodium falciparum (25), flies (26), zebrafish (27), Arabidopsis thaliana (28), mice (29,30), and humans (30)(31)(32)(33)(34)(35). Most of these studies were conducted in vivo, and therefore do not allow for isolation of effects encoded into the genomic sequences.…”

Section: Introductionmentioning

confidence: 99%

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Genomes of Multicellular Organisms Have Evolved to Attract Nucleosomes to Promoter Regions

Tompitak

Vaillant

Schiessel

2017

Biophysical Journal

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Sequences that influence nucleosome positioning in promoter regions, and their relation to gene regulation, have been the topic of much research over the last decade. In yeast, significant nucleosome-depleted regions are found, which facilitate transcription. With the arrival of nucleosome positioning maps for the human genome, it was discovered that in our genome, unlike in that of yeast, promoters encode for high nucleosome occupancy. In this work, we look at the genomes of a range of different organisms, to provide a catalog of nucleosome positioning signals in promoters across the tree of life. We utilize a computational model of the nucleosome, based on crystallographic analyses of the structure and elasticity of the nucleosome, to predict the nucleosome positioning signals in promoter regions. To be able to apply our model to large genomic datasets, we introduce an approximative scheme that makes use of the limited range of correlations in nucleosomal sequence preferences to create a computationally efficient approximation of the full biophysical model. Our predictions show that a clear distinction between unicellular and multicellular life is visible in the intrinsically encoded nucleosome affinity. Furthermore, the strength of the nucleosome positioning signals correlates with the complexity of the organism. We conclude that encoding for high nucleosome occupancy, as in the human genome, is in fact a universal feature of multicellular life.

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Section: Resultsmentioning

confidence: 96%

Section: Data Acquisitionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genomes of Multicellular Organisms Have Evolved to Attract Nucleosomes to Promoter Regions

Tompitak

Vaillant

Schiessel

2017

Biophysical Journal

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“…In higher eukaryotes, the DNA sequence at promoters, enhancers, and transcription factor-binding sites generally encode a high intrinsic nucleosome occupancy (Tillo et al 2010;Gaffney et al 2012). However, in disagreement with predicted high nucleosome occupancy, genome-wide mapping typically shows that nucleosomes are depleted at active promoters (Schones et al 2008;Valouev et al 2011;Teif et al 2012). DNA accessibility studies further indicate that promoters tend to open ubiquitously among multiple cell types (Thurman et al 2012), suggesting that generally expressed trans-factors keep promoters accessible.…”

Section: Nucleosomes At Enhancers: a Collaborator For Pioneer Factorsmentioning

confidence: 99%

Pioneer transcription factors in cell reprogramming

2014

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A subset of eukaryotic transcription factors possesses the remarkable ability to reprogram one type of cell into another. The transcription factors that reprogram cell fate are invariably those that are crucial for the initial cell programming in embryonic development. To elicit cell programming or reprogramming, transcription factors must be able to engage genes that are developmentally silenced and inappropriate for expression in the original cell. Developmentally silenced genes are typically embedded in ''closed'' chromatin that is covered by nucleosomes and not hypersensitive to nuclease probes such as DNase I. Biochemical and genomic studies have shown that transcription factors with the highest reprogramming activity often have the special ability to engage their target sites on nucleosomal DNA, thus behaving as ''pioneer factors'' to initiate events in closed chromatin. Other reprogramming factors appear dependent on pioneer factors for engaging nucleosomes and closed chromatin. However, certain genomic domains in which nucleosomes are occluded by higher-order chromatin structures, such as in heterochromatin, are resistant to pioneer factor binding. Understanding the means by which pioneer factors can engage closed chromatin and how heterochromatin can prevent such binding promises to advance our ability to reprogram cell fates at will and is the topic of this review.Cell fate control represents the most extreme form of gene regulation. Genes specific to the function of a particular type of cell may be antagonistic to the function of another type of cell, so nature has evolved diverse regulatory mechanisms to ensure stable patterns of gene activation and repression. In prokaryotes, self-sustaining regulatory networks of transcription factors bound to DNA can be sufficient to regulate gene activation and repression (Ptashne 2011). In eukaryotes, ;200-base-pair (bp) segments of the genome are wound nearly twice around an octamer of the four core histones to form nucleosomes, providing steric constraints on how transcription factors can bind DNA (Kornberg and Lorch 1999). As described below, pioneer transcription factors have the special property of being able to overcome such constraints, enabling the factors to engage closed chromatin that is not accessible by other types of transcription factors (Fig. 1). However, further higher-order packaging of nucleosomes into heterochromatin can occlude access to DNA altogether, presenting an additional barrier to cell fate conversion (Fig. 1). This review focuses on the most recent studies of pioneer factors in cell programming and reprogramming, how pioneer factors have special chromatinbinding properties, and facilitators and impediments to chromatin binding. We project that such knowledge will greatly aid future efforts to change the fates of cells at will for research, diagnostic, and therapeutic purposes.

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ATAC‐seq: A Method for Assaying Chromatin Accessibility Genome‐Wide

Buenrostro

Chang

et al. 2015

CP Molecular Biology

2,826

2,496

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This unit describes Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq), a method for mapping chromatin accessibility genome-wide. This method probes DNA accessibility with hyperactive Tn5 transposase, which inserts sequencing adapters into accessible regions of chromatin. Sequencing reads can then be used to infer regions of increased accessibility, as well as to map regions of transcription factor binding and nucleosome position. The method is a fast and sensitive alternative to DNase-Seq for assaying chromatin accessibility genome-wide, or to MNase for assaying nucleosome positions in accessible regions of the genome.

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Determinants of nucleosome organization in primary human cells

Cited by 612 publications

References 34 publications

Genomes of Multicellular Organisms Have Evolved to Attract Nucleosomes to Promoter Regions

Genomes of Multicellular Organisms Have Evolved to Attract Nucleosomes to Promoter Regions

Pioneer transcription factors in cell reprogramming

ATAC‐seq: A Method for Assaying Chromatin Accessibility Genome‐Wide

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