Nucleosome positioning: bringing order to the eukaryotic genome. Trends Cell Biol

Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, and Section of Molecular Genetics and Microbiology, University of Texas at Austin, 1 University Station A4800, Austin, TX 78712-0159, USA.
Trends in cell biology (Impact Factor: 12.31). 03/2012; 22(5):250-6. DOI: 10.1016/j.tcb.2012.02.004
Source: PubMed

ABSTRACT Nucleosomes are an essential component of eukaryotic chromosomes. The impact of nucleosomes is seen not just on processes that directly access the genome, such as transcription, but also on an evolutionary timescale. Recent studies in various organisms have provided high-resolution maps of nucleosomes throughout the genome. Computational analysis, in conjunction with many other kinds of data, has shed light on several aspects of nucleosome biology. Nucleosomes are positioned by several means, including intrinsic sequence biases, by stacking against a fixed barrier, by DNA-binding proteins and by chromatin remodelers. These studies underscore the important organizational role of nucleosomes in all eukaryotic genomes. This paper reviews recent genomic studies that have shed light on the determinants of nucleosome positioning and their impact on the genome.

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    • "Unlike the IFN genes, these nucleosomes do not obscure the transcriptional start site, and an appropriate NDR is maintained that allows unhindered Pol II engagement. The mechanisms governing nucleosome positioning have been intensely studied and debated (Segal and Widom 2009; Iyer 2012), but current models acknowledge that both intrinsic nucleosome DNA sequence preferences (Brogaard and others 2012; Gaffney and others 2012) and sequence-independent processes (Zhang and Pugh 2011; Yen and others 2012) participate in guiding nucleosomes to and from DNA destinations . The IFN locus reflects both of these phenomena. "
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    ABSTRACT: Genome-wide investigations have dramatically increased our understanding of nucleosome positioning and the role of chromatin in gene regulation, yet some genomic regions have been poorly represented in human nucleosome maps. One such region is represented by human chromosome 9p21-22, which contains the type I interferon gene cluster that includes 16 interferon alpha genes and the single interferon beta, interferon epsilon, and interferon omega genes. A high-density nucleosome mapping strategy was used to generate locus-wide maps of the nucleosome organization of this biomedically important locus at a steady state and during a time course of infection with Sendai virus, an inducer of interferon gene expression. Detailed statistical and computational analysis illustrates that nucleosomes in this locus exhibit preferences for particular dinucleotide and oligomer DNA sequence motifs in vivo, which are similar to those reported for lower eukaryotic nucleosome-DNA interactions. These data were used to visualize the region's chromatin architecture and reveal features that are common to the organization of all the type I interferon genes, indicating a common nucleosome-mediated gene regulatory paradigm. Additionally, this study clarifies aspects of the dynamic changes that occur with the nucleosome occupying the transcriptional start site of the interferon beta gene after virus infection.
    Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 03/2014; 34(9). DOI:10.1089/jir.2013.0118 · 3.90 Impact Factor
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    • "Because DDM1 can remodel nucleosomes, we asked whether chromatin features are responsible for the differential requirement of DDM1 for DNA methylation. Sequence composition is thought to be a major determinant of the nucleosome landscape (Iyer, 2012); indeed, ddm1 TE demethylation in all sequence contexts is strongly correlated with nucleosome occupancy and GC content (Figure 2A). Short TEs and TE edges are relatively AT rich and nucleosome depleted (Figures 2B, 2C, and S2A), consistent with the preferential requirement of DDM1 to maintain DNA methylation in the bodies of long TEs (Figures 1E, 1F, and 2A). "
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    ABSTRACT: Nucleosome remodelers of the DDM1/Lsh family are required for DNA methylation of transposable elements, but the reason for this is unknown. How DDM1 interacts with other methylation pathways, such as small-RNA-directed DNA methylation (RdDM), which is thought to mediate plant asymmetric methylation through DRM enzymes, is also unclear. Here, we show that most asymmetric methylation is facilitated by DDM1 and mediated by the methyltransferase CMT2 separately from RdDM. We find that heterochromatic sequences preferentially require DDM1 for DNA methylation and that this preference depends on linker histone H1. RdDM is instead inhibited by heterochromatin and absolutely requires the nucleosome remodeler DRD1. Together, DDM1 and RdDM mediate nearly all transposon methylation and collaborate to repress transposition and regulate the methylation and expression of genes. Our results indicate that DDM1 provides DNA methyltransferases access to H1-containing heterochromatin to allow stable silencing of transposable elements in cooperation with the RdDM pathway.
    Cell 03/2013; 153(1):193-205. DOI:10.1016/j.cell.2013.02.033 · 33.12 Impact Factor
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    • "Recently, the first question received abundant answers as nucleosomes were mapped genome-wide in many species (Yuan et al, 2005; Mavrich et al, 2008; Valouev et al, 2008; Lantermann et al, 2010; Valouev et al, 2011). This revealed that a major portion of nucleosomes indeed adopts well-defined positions, especially in regions that are important for regulation, like promoters and replication origins (Jiang and Pugh, 2009; Radman-Livaja and Rando, 2010; Iyer, 2012). Particularly at gene starts there is often a stereotypic organization with a broad (B150–200 bp) nucleosome free region (NFR) just upstream of the transcription start site (TSS) that is flanked by highly positioned nucleosomes ( þ 1, sometimes also À 1 nucleosome). "
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    ABSTRACT: Nucleosome positioning governs access to eukaryotic genomes. Many genes show a stereotypic organisation at their 5'end: a nucleosome free region just upstream of the transcription start site (TSS) followed by a regular nucleosomal array over the coding region. The determinants for this pattern are unclear, but nucleosome remodelers are likely critical. Here we study the role of remodelers in global nucleosome positioning in S. pombe and the corresponding changes in expression. We find a striking evolutionary shift in remodeler usage between budding and fission yeast. The S. pombe RSC complex does not seem to be involved in nucleosome positioning, despite its prominent role in S. cerevisiae. While S. pombe lacks ISWI-type remodelers, it has two CHD1-type ATPases, Hrp1 and Hrp3. We demonstrate nucleosome spacing activity for Hrp1 and Hrp3 in vitro, and that together they are essential for linking regular genic arrays to most TSSs in vivo. Impaired arrays in the absence of either or both remodelers may lead to increased cryptic antisense transcription, but overall gene expression levels are only mildly affected.
    The EMBO Journal 10/2012; 31(23). DOI:10.1038/emboj.2012.289 · 10.75 Impact Factor
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