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: 12.01). 03/2012; 22(5):250-6. DOI: 10.1016/j.tcb.2012.02.004
Source: PubMed


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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    • "Genomic nucleosome positioning is determined by a combination of specific DNA sequences, chromatin remodelers , sequence-specific DNA binding proteins, and modifications in DNA and histones, all of which facilitate entrapment of nucleosomes at specific sites (Choi and Kim, 2009; Sadeh and Allis, 2011; Struhl and Segal, 2013). Sequences occupied by nucleosomes are usually refractory to binding by other factors, which implies that chromatin serves as the template for interpreting the DNA regulatory code that suppresses genetic and/or environmental perturbations and affects phenotypic variation (Cairns, 2009; Jiang and Pugh, 2009; Wang et al., 2011; Iyer, 2012; Luger et al., 2012). Histone variants contribute to chromatin complexity by creating specialized nucleosomes, which when situated on DNA regulatory elements can have profound effects on nucleosome stability, protein accessibility to DNA, and cellular longevity (Campos and Reinberg, 2009; Talbert and Henikoff, 2010). "
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    ABSTRACT: The histone variant macroH2A (mH2A) has been implicated in transcriptional repression, but the molecular mechanisms that contribute to global mH2A-dependent genome regulation remain elusive. Using chromatin immunoprecipitation sequencing (ChIP-seq) coupled with transcriptional profiling in mH2A knockdown cells, we demonstrate that singular mH2A nucleosomes occupy transcription start sites of subsets of both expressed and repressed genes, with opposing regulatory consequences. Specifically, mH2A nucleosomes mask repressor binding sites in expressed genes but activator binding sites in repressed genes, thus generating distinct chromatin landscapes that limit genetic or extracellular inductive signals. We show that composite nucleosomes containing mH2A and NRF-1 are stably positioned on gene regulatory regions and can buffer transcriptional noise associated with antiviral responses. In contrast, mH2A nucleosomes without NRF-1 bind promoters weakly and mark genes with noisier gene expression patterns. Thus, the strategic position and stabilization of mH2A nucleosomes in human promoters defines robust gene expression patterns.
    Cell Reports 05/2015; 11:1090-1101. DOI:10.1016/j.celrep.2015.04.022 · 8.36 Impact Factor
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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 · 2.00 Impact Factor
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    • "A core promoter in yeast is situated within a nucleosome-depleted region (NDR) and is followed by a well-aligned array of nucleosomes starting from the TSS (36). This property of nucleosome organization allowed us to test the accuracy of TSS calls by examining their relationship to nucleosome profiles. "
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    ABSTRACT: Understanding the relationships between regulatory factor binding, chromatin structure, cis-regulatory elements and RNA-regulation mechanisms relies on accurate information about transcription start sites (TSS) and polyadenylation sites (PAS). Although several approaches have identified transcript ends in yeast, limitations of resolution and coverage have remained, and definitive identification of TSS and PAS with single-nucleotide resolution has not yet been achieved. We developed SMORE-seq (simultaneous mapping of RNA ends by sequencing) and used it to simultaneously identify the strongest TSS for 5207 (90%) genes and PAS for 5277 (91%) genes. The new transcript annotations identified by SMORE-seq showed improved distance relationships with TATA-like regulatory elements, nucleosome positions and active RNA polymerase. We found 150 genes whose TSS were downstream of the annotated start codon, and additional analysis of evolutionary conservation and ribosome footprinting suggests that these protein-coding sequences are likely to be mis-annotated. SMORE-seq detected short non-coding RNAs transcribed divergently from more than a thousand promoters in wild-type cells under normal conditions. These divergent non-coding RNAs were less evident at promoters containing canonical TATA boxes, suggesting a model where transcription initiation at promoters by RNAPII is bidirectional, with TATA elements serving to constrain the directionality of initiation.
    Nucleic Acids Research 01/2014; 42(6). DOI:10.1093/nar/gkt1366 · 9.11 Impact Factor
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