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  • 1
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    The DNA-encoded nucleosome organization of a eukaryotic genome (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-12-19
    Description: Nucleosome organization is critical for gene regulation. In living cells this organization is determined by multiple factors, including the action of chromatin remodellers, competition with site-specific DNA-binding proteins, and the DNA sequence preferences of the nucleosomes themselves. However, it has been difficult to estimate the relative importance of each of these mechanisms in vivo, because in vivo nucleosome maps reflect the combined action of all influencing factors. Here we determine the importance of nucleosome DNA sequence preferences experimentally by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map, in which nucleosome occupancy is governed only by the intrinsic sequence preferences of nucleosomes, is similar to in vivo nucleosome maps generated in three different growth conditions. In vitro, nucleosome depletion is evident at many transcription factor binding sites and around gene start and end sites, indicating that nucleosome depletion at these sites in vivo is partly encoded in the genome. We confirm these results with a micrococcal nuclease-independent experiment that measures the relative affinity of nucleosomes for approximately 40,000 double-stranded 150-base-pair oligonucleotides. Using our in vitro data, we devise a computational model of nucleosome sequence preferences that is significantly correlated with in vivo nucleosome occupancy in Caenorhabditis elegans. Our results indicate that the intrinsic DNA sequence preferences of nucleosomes have a central role in determining the organization of nucleosomes in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658732/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658732/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaplan, Noam -- Moore, Irene K -- Fondufe-Mittendorf, Yvonne -- Gossett, Andrea J -- Tillo, Desiree -- Field, Yair -- LeProust, Emily M -- Hughes, Timothy R -- Lieb, Jason D -- Widom, Jonathan -- Segal, Eran -- R01 CA119176/CA/NCI NIH HHS/ -- R01 CA119176-03/CA/NCI NIH HHS/ -- R01 GM054692/GM/NIGMS NIH HHS/ -- R01 GM054692-11/GM/NIGMS NIH HHS/ -- R01 GM058617/GM/NIGMS NIH HHS/ -- R01 GM058617-11/GM/NIGMS NIH HHS/ -- R01 GM072518/GM/NIGMS NIH HHS/ -- R01 GM072518-01A1/GM/NIGMS NIH HHS/ -- R01 GM072518-02/GM/NIGMS NIH HHS/ -- R01 GM072518-03/GM/NIGMS NIH HHS/ -- R01 GM072518-04/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Mar 19;458(7236):362-6. doi: 10.1038/nature07667. Epub 2008 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19092803" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Caenorhabditis elegans/genetics ; Chickens ; Computational Biology ; Computer Simulation ; Eukaryotic Cells/*metabolism ; Genome, Fungal/*genetics ; Micrococcal Nuclease/metabolism ; Nucleosomes/*genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Saccharomyces cerevisiae/*genetics/growth & development ; Sequence Analysis, DNA ; Transcription Factors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Nucleosome maps of the human cytomegalovirus genome reveal a temporal switch in chromatin organization linked to a major IE protein (2013)
    National Academy of Sciences
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    Publication Date: 2013-07-22
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 3
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    Methylated Cytosines Mutate to Transcription Factor Binding Sites that Drive Tetrapod Evolution (2015)
    Oxford University Press
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    Publication Date: 2015-11-30
    Description: In mammals, the cytosine in CG dinucleotides is typically methylated producing 5-methylcytosine (5mC), a chemically less stable form of cytosine that can spontaneously deaminate to thymidine resulting in a T•G mismatched base pair. Unlike other eukaryotes that efficiently repair this mismatched base pair back to C•G, in mammals, 5mCG deamination is mutagenic, sometimes producing TG dinucleotides, explaining the depletion of CG dinucleotides in mammalian genomes. It was suggested that new TG dinucleotides generate genetic diversity that may be critical for evolutionary change. We tested this conjecture by examining the DNA sequence properties of regulatory sequences identified by DNase I hypersensitive sites (DHSs) in human and mouse genomes. We hypothesized that the new TG dinucleotides generate transcription factor binding sites (TFBS) that become tissue-specific DHSs (TS-DHSs). We find that 8-mers containing the CG dinucleotide are enriched in DHSs in both species. However, 8-mers containing a TG and no CG dinucleotide are preferentially enriched in TS-DHSs when compared with 8-mers with neither a TG nor a CG dinucleotide. The most enriched 8-mer with a TG and no CG dinucleotide in tissue-specific regulatory regions in both genomes is the AP-1 motif ( TG A C / G T CA N), and we find evidence that TG dinucleotides in the AP-1 motif arose from CG dinucleotides. Additional TS-DHS-enriched TFBS containing the TG/CA dinucleotide are the E-Box motif (G CA GC TG C), the NF-1 motif (GG CA—TG CC), and the GR (glucocorticoid receptor) motif (G-A CA—TG T-C). Our results support the suggestion that cytosine methylation is mutagenic in tetrapods producing TG dinucleotides that create TFBS that drive evolution.
    Electronic ISSN: 1759-6653
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    Nucleosome organization of the hCMV genome [Microbiology] (2013)
    National Academy of Sciences
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    Publication Date: 2013-08-07
    Description: Human CMV (hCMV) establishes lifelong infections in most of us, causing developmental defects in human embryos and life-threatening disease in immunocompromised individuals. During productive infection, the viral 〉230,000-bp dsDNA genome is expressed widely and in a temporal cascade. The hCMV genome does not carry histones when encapsidated but has been...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 5
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    GABP{alpha} Binding to Overlapping ETS and CRE DNA Motifs Is Enhanced by CREB1: Custom DNA Microarrays (2015)
    Genetics Society of America (GSA)
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    Publication Date: 2015-09-02
    Description: To achieve proper spatiotemporal control of gene expression, transcription factors cooperatively assemble onto specific DNA sequences. The ETS domain protein monomer of GABPα and the B-ZIP domain protein dimer of CREB1 cooperatively bind DNA only when the ETS ( C / G CGGAA GT ) and CRE ( GT GACGTCAC) motifs overlap precisely, producing the ETSCRE motif ( C / G CGGAA GT GACGTCAC). We designed a Protein Binding Microarray (PBM) with 60-bp DNAs containing four identical sectors, each with 177,440 features that explore the cooperative interactions between GABPα and CREB1 upon binding the ETSCRE motif. The DNA sequences include all 15-mers of the form C / G CGGA—–CG—, the ETSCRE motif, and all single nucleotide polymorphisms (SNPs), and occurrences in the human and mouse genomes. CREB1 enhanced GABPα binding to the canonical ETSCRE motif CCGGAAGT two-fold, and up to 23-fold for several SNPs at the beginning and end of the ETS motif, which is suggestive of two separate and distinct allosteric mechanisms of cooperative binding. We show that the ETS-CRE array data can be used to identify regions likely cooperatively bound by GABPα and CREB1 in vivo , and demonstrate their ability to identify human genetic variants that might inhibit cooperative binding.
    Electronic ISSN: 2160-1836
    Topics: Biology
    Published by Genetics Society of America (GSA)
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