Large-Scale Turnover of Functional Transcription Factor Binding Sites in Drosophila
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{"title"=>"Large-scale turnover of functional transcription factor binding sites in Drosophila", "type"=>"journal", "authors"=>[{"first_name"=>"Alan M.", "last_name"=>"Moses", "scopus_author_id"=>"56839913500"}, {"first_name"=>"Daniel A.", "last_name"=>"Pollard", "scopus_author_id"=>"7103394638"}, {"first_name"=>"David A.", "last_name"=>"Nix", "scopus_author_id"=>"7006132266"}, {"first_name"=>"Venky N.", "last_name"=>"Iyer", "scopus_author_id"=>"9746295800"}, {"first_name"=>"Xiao Yong", "last_name"=>"Li", "scopus_author_id"=>"55718273300"}, {"first_name"=>"Mark D.", "last_name"=>"Biggin", "scopus_author_id"=>"7004823673"}, {"first_name"=>"Michael B.", "last_name"=>"Eisen", "scopus_author_id"=>"7004331829"}], "year"=>2006, "source"=>"PLoS Computational Biology", "identifiers"=>{"pui"=>"44656516", "issn"=>"1553734X", "isbn"=>"1553-7358 (Electronic)", "doi"=>"10.1371/journal.pcbi.0020130", "scopus"=>"2-s2.0-33750442876", "pmid"=>"17040121", "sgr"=>"33750442876"}, "id"=>"739dd55b-d4c9-39da-a536-8551a47f57d2", "abstract"=>"The gain and loss of functional transcription factor binding sites has been proposed as a major source of evolutionary change in cis-regulatory DNA and gene expression. We have developed an evolutionary model to study binding-site turnover that uses multiple sequence alignments to assess the evolutionary constraint on individual binding sites, and to map gain and loss events along a phylogenetic tree. We apply this model to study the evolutionary dynamics of binding sites of the Drosophila melanogaster transcription factor Zeste, using genome-wide in vivo (ChIP-chip) binding data to identify functional Zeste binding sites, and the genome sequences of D. melanogaster, D. simulans, D. erecta, and D. yakuba to study their evolution. We estimate that more than 5% of functional Zeste binding sites in D. melanogaster were gained along the D. melanogaster lineage or lost along one of the other lineages. We find that Zeste-bound regions have a reduced rate of binding-site loss and an increased rate of binding-site gain relative to flanking sequences. Finally, we show that binding-site gains and losses are asymmetrically distributed with respect to D. melanogaster, consistent with lineage-specific acquisition and loss of Zeste-responsive regulatory elements.", "link"=>"http://www.mendeley.com/research/largescale-turnover-functional-transcription-factor-binding-sites-drosophila", "reader_count"=>171, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>21, "Student > Doctoral Student"=>4, "Researcher"=>50, "Student > Ph. D. Student"=>60, "Student > Postgraduate"=>2, "Student > Master"=>12, "Other"=>2, "Student > Bachelor"=>6, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>2, "Professor"=>11}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>21, "Student > Doctoral Student"=>4, "Researcher"=>50, "Student > Ph. D. Student"=>60, "Student > Postgraduate"=>2, "Student > Master"=>12, "Other"=>2, "Student > Bachelor"=>6, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>2, "Professor"=>11}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>2, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>15, "Agricultural and Biological Sciences"=>133, "Medicine and Dentistry"=>1, "Neuroscience"=>1, "Physics and Astronomy"=>3, "Chemistry"=>1, "Computer Science"=>11, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>133}, "Computer Science"=>{"Computer Science"=>11}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>15}, "Unspecified"=>{"Unspecified"=>2}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"Canada"=>3, "Argentina"=>1, "Hong Kong"=>1, "United States"=>13, "United Kingdom"=>4, "Australia"=>1, "France"=>2, "Chile"=>1, "Germany"=>1, "Spain"=>1, "India"=>1, "Indonesia"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/955836"], "description"=>"<div><p>(A) The binding specificity of Zeste derived from known Zeste binding sites in the D. melanogaster genome [<a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0020130#pcbi-0020130-b037\" target=\"_blank\">37</a>], depicted as a “sequence logo” [<a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0020130#pcbi-0020130-b063\" target=\"_blank\">63</a>], constructed using <a href=\"http://ep.ebi.ac.uk/EP/SEQLOGO\" target=\"_blank\">http://ep.ebi.ac.uk/EP/SEQLOGO</a>.</p><p>(B) Variation in the rate of evolution at each position in predicted Zeste binding sites found in Zeste-bound regions (unfilled squares) along with predictions of the HB model (filled squares) or the HKY model (grey squares). The rates are correlated with the HB predictions, but are faster. See text for details.</p><p>(C,D) Examination of the rates of different types of substitutions at positions 2 (C) and 3 (D) within the Zeste binding site shows that the observed rates (unfilled bars) are generally between the predictions of the HB model (filled bars) and the HKY model (grey bars).</p></div>", "links"=>[], "tags"=>["patterns", "zeste", "binding"], "article_id"=>626114, "categories"=>["Biological Sciences", "Medicine", "Developmental Biology"], "users"=>["Alan M Moses", "Daniel A Pollard", "David A Nix", "Venky N Iyer", "Xiao-Yong Li", "Mark D Biggin", "Michael B Eisen"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.0020130.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rates_and_Patterns_of_Evolution_in_Zeste_Binding_Sites_/626114", "title"=>"Rates and Patterns of Evolution in Zeste Binding Sites", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:08:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/956150"], "description"=>"<div><p>(A) Configurations of binding sites in the four species where we can infer a single gain (i–iv) or loss (v–vii) event. There are an additional two situations where we can infer that only a single event occurred, but we cannot distinguish a loss from a gain; and an additional four scenarios that are not consistent with a single event.</p><p>ere, <i>D. erecta;</i> mel, <i>D. melanogaster;</i> sim, <i>D. simulans;</i> yak, D. yakuba.</p><p>(B) Schematic representation of a model for evolution at the level of binding sites. Selection could lead to an excess in the number of binding sites by increasing the rate of binding-site gain, by decreasing the rate of binding-site loss, or both. Indicated are the relative rates of gain and loss in the bound regions compared with the flanking noncoding regions; that the relative rate of loss is less than one suggests the action of purifying selection to retain binding sites. That the relative rate of gain is greater than one is consistent with selection or functional drift. See text for details.</p><p>(C) The fraction of gains, losses, and net change in binding-site number (grey bars) along the D. melanogaster lineage are respectively greater, less, and greater than the expectation based on the phylogenetic tree (dashed line). This is expected if there has been lineage-specific evolution of function, but not if all changes are compensatory. See text for further discussion. Error bars represent the standard error of the proportion.</p><p>(D) The distribution of the number of “co-occurring pairs” of complementary nonconserved binding sites in 1,000 random permutations (grey bars). Compensatory changes imply an excess of co-occurring sites, but the observed value (black bar) does not fall in the extreme of this distribution.</p></div>", "links"=>[], "tags"=>["binding-site"], "article_id"=>626425, "categories"=>["Biological Sciences", "Medicine", "Developmental Biology"], "users"=>["Alan M Moses", "Daniel A Pollard", "David A Nix", "Venky N Iyer", "Xiao-Yong Li", "Mark D Biggin", "Michael B Eisen"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.0020130.g006", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Testing_Models_of_Binding_Site_Turnover_/626425", "title"=>"Testing Models of Binding-Site Turnover", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:10:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/955764"], "description"=>"<p>Raw hybridization intensities for oligonucleotide probes in (A) the muscleblind (mbl) locus on chromosome 2R and (B) zeste (z) locus on the X chromosome. Coordinates are from D. melanogaster release 4.0; annotations from D. melanogaster release 4.2. Black bars show individual oligo hybridization intensities for two independent immunoprecipitations and hybridizations (z1 and z2). Note the high degree of reproducibility in the data. The location of bound intervals (see text) is shown as blue boxes, and the oligonucleotides corresponding to the identified binding peaks are colored red. In (B), the position of known zeste footprints [<a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0020130#pcbi-0020130-b037\" target=\"_blank\">37</a>] is indicated by an *.</p>", "links"=>[], "tags"=>["vivo", "binding"], "article_id"=>626041, "categories"=>["Biological Sciences", "Medicine", "Developmental Biology"], "users"=>["Alan M Moses", "Daniel A Pollard", "David A Nix", "Venky N Iyer", "Xiao-Yong Li", "Mark D Biggin", "Michael B Eisen"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.0020130.g001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_Vivo_Binding_of_Zeste_/626041", "title"=>"In Vivo Binding of Zeste", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:08:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/955976"], "description"=>"<div><p>(A) The probability density function of the T statistic under either the HB (black trace) or HKY (grey trace) model of evolution calculated as per [<a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0020130#pcbi-0020130-b039\" target=\"_blank\">39</a>,<a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0020130#pcbi-0020130-b064\" target=\"_blank\">64</a>] and averaged in windows of 100 adjacent scores. The traces are slightly jagged, reflecting the fact that these distributions are discrete.</p><p>(B) The fraction of predicted Zeste binding sites in the bound regions as a function of the value of the T statistic. See text for details. Dotted lines bound the area corresponding to <i>p</i> = 0.01 under the null hypothesis of HB evolution.</p></div>", "links"=>[], "tags"=>["statistic", "binding", "sites", "patterns"], "article_id"=>626250, "categories"=>["Biological Sciences", "Medicine", "Developmental Biology"], "users"=>["Alan M Moses", "Daniel A Pollard", "David A Nix", "Venky N Iyer", "Xiao-Yong Li", "Mark D Biggin", "Michael B Eisen"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.0020130.g004", "stats"=>{"downloads"=>2, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_Statistic_to_Classify_Binding_Sites_Based_on_Patterns_of_Evolution_/626250", "title"=>"A Statistic to Classify Binding Sites Based on Patterns of Evolution", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:09:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/956093"], "description"=>"<p>The average number of nonconserved Zeste binding sites per kb within 300 bp of peaks in the bound regions (unfilled bars) and the flanking noncoding regions (grey bars). The threshold <i>p</i> = 0.01 was used for the T statistic with the HB model as the null distribution to identify nonconserved binding sites. As a control for base composition, rate of evolution, or other local sequence effects, the numbers of nonconserved matches to a scrambled version of the Zeste specificity matrix in the same regions are also shown. Error bars represent the standard error of the proportion.</p>", "links"=>[], "tags"=>["nonconserved", "binding", "sites", "enriched", "bound"], "article_id"=>626364, "categories"=>["Biological Sciences", "Medicine", "Developmental Biology"], "users"=>["Alan M Moses", "Daniel A Pollard", "David A Nix", "Venky N Iyer", "Xiao-Yong Li", "Mark D Biggin", "Michael B Eisen"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.0020130.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_Nonconserved_Binding_Sites_Are_Enriched_in_Bound_Regions_/626364", "title"=>"Functional Nonconserved Binding Sites Are Enriched in Bound Regions", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:10:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/470488", "https://ndownloader.figshare.com/files/470504", "https://ndownloader.figshare.com/files/470513"], "description"=>"<div><p>The gain and loss of functional transcription factor binding sites has been proposed as a major source of evolutionary change in <em>cis-</em>regulatory DNA and gene expression. We have developed an evolutionary model to study binding-site turnover that uses multiple sequence alignments to assess the evolutionary constraint on individual binding sites, and to map gain and loss events along a phylogenetic tree. We apply this model to study the evolutionary dynamics of binding sites of the Drosophila melanogaster transcription factor Zeste, using genome-wide in vivo (ChIP–chip) binding data to identify functional Zeste binding sites, and the genome sequences of D. melanogaster, D. simulans, <em>D. erecta,</em> and D. yakuba to study their evolution. We estimate that more than 5% of functional Zeste binding sites in D. melanogaster were gained along the D. melanogaster lineage or lost along one of the other lineages. We find that Zeste-bound regions have a reduced rate of binding-site loss and an increased rate of binding-site gain relative to flanking sequences. Finally, we show that binding-site gains and losses are asymmetrically distributed with respect to D. melanogaster, consistent with lineage-specific acquisition and loss of Zeste-responsive regulatory elements.</p></div>", "links"=>[], "tags"=>["large-scale", "turnover", "transcription", "binding", "sites"], "article_id"=>152765, "categories"=>["Biological Sciences", "Medicine", "Developmental Biology"], "users"=>["Alan M Moses", "Daniel A Pollard", "David A Nix", "Venky N Iyer", "Xiao-Yong Li", "Mark D Biggin", "Michael B Eisen"], "doi"=>["https://dx.doi.org/10.1371/journal.pcbi.0020130.sd001", "https://dx.doi.org/10.1371/journal.pcbi.0020130.sd002", "https://dx.doi.org/10.1371/journal.pcbi.0020130.sg001"], "stats"=>{"downloads"=>9, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Large_Scale_Turnover_of_Functional_Transcription_Factor_Binding_Sites_in_Drosophila_/152765", "title"=>"Large-Scale Turnover of Functional Transcription Factor Binding Sites in <em>Drosophila</em>", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2006-10-13 00:46:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/955899"], "description"=>"<div><p>(A) Two experimentally characterized [<a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0020130#pcbi-0020130-b037\" target=\"_blank\">37</a>] Zeste binding sites in the <i>z</i> promoter for which we cannot reject the hypothesis that the binding sites are evolving under the HBZ model using the T statistic.</p><p>(B) Four experimentally characterized [<a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0020130#pcbi-0020130-b034\" target=\"_blank\">34</a>–<a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0020130#pcbi-0020130-b036\" target=\"_blank\">36</a>] Zeste binding sites the Ubx promoter for which we can reject the hypothesis that the binding sites are evolving under the HBZ model using the T statistic. In the species missing orthologous binding sites for (i) and (ii), we find predicted Zeste binding sites on the opposite strand in approximately the same locations, consistent with compensatory evolution. For (iii) and (iv) there are no such obvious replacements, suggestive of lineage-specific evolution.</p><p>T values and associated <i>p</i>-values are indicated beneath each binding site. Bold, red type indicates the region bound by Zeste in vitro in footprinting assays. Blue boxes indicate matches to the Zeste matrix. Black boxes indicate matches to the matrix not found in D. melanogaster.</p><p>ere, <i>D. erecta;</i> mel, <i>D. melanogaster;</i> sim, <i>D. simulans;</i> yak, D. yakuba.</p></div>", "links"=>[], "tags"=>["zeste", "binding", "sites", "ubx"], "article_id"=>626174, "categories"=>["Biological Sciences", "Medicine", "Developmental Biology"], "users"=>["Alan M Moses", "Daniel A Pollard", "David A Nix", "Venky N Iyer", "Xiao-Yong Li", "Mark D Biggin", "Michael B Eisen"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.0020130.g003", "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evolution_of_Zeste_Binding_Sites_in_the_z_and_Ubx_Promoters_/626174", "title"=>"Evolution of Zeste Binding Sites in the <i>z</i> and Ubx Promoters", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:09:03"}

PMC Usage Stats | Further Information

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Relative Metric

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