Evolution and Genetic Architecture of Chromatin Accessibility and Function in Yeast
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{"title"=>"Evolution and Genetic Architecture of Chromatin Accessibility and Function in Yeast", "type"=>"journal", "authors"=>[{"first_name"=>"Caitlin F.", "last_name"=>"Connelly", "scopus_author_id"=>"34871640100"}, {"first_name"=>"Jon", "last_name"=>"Wakefield", "scopus_author_id"=>"7102220857"}, {"first_name"=>"Joshua M.", "last_name"=>"Akey", "scopus_author_id"=>"6601938072"}], "year"=>2014, "source"=>"PLoS Genetics", "identifiers"=>{"pmid"=>"24992477", "doi"=>"10.1371/journal.pgen.1004427", "sgr"=>"84905454828", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "scopus"=>"2-s2.0-84905454828", "issn"=>"15537404", "pui"=>"373701211"}, "id"=>"8a908571-34b7-3f73-9aa4-1f289b07361a", "abstract"=>"Chromatin accessibility is an important functional genomics phenotype that influences transcription factor binding and gene expression. Genome-scale technologies allow chromatin accessibility to be mapped with high-resolution, facilitating detailed analyses into the genetic architecture and evolution of chromatin structure within and between species. We performed Formaldehyde-Assisted Isolation of Regulatory Elements sequencing (FAIRE-Seq) to map chromatin accessibility in two parental haploid yeast species, Saccharomyces cerevisiae and Saccharomyces paradoxus and their diploid hybrid. We show that although broad-scale characteristics of the chromatin landscape are well conserved between these species, accessibility is significantly different for 947 regions upstream of genes that are enriched for GO terms such as intracellular transport and protein localization exhibit. We also develop new statistical methods to investigate the genetic architecture of variation in chromatin accessibility between species, and find that cis effects are more common and of greater magnitude than trans effects. Interestingly, we find that cis and trans effects at individual genes are often negatively correlated, suggesting widespread compensatory evolution to stabilize levels of chromatin accessibility. Finally, we demonstrate that the relationship between chromatin accessibility and gene expression levels is complex, and a significant proportion of differences in chromatin accessibility might be functionally benign.", "link"=>"http://www.mendeley.com/research/evolution-genetic-architecture-chromatin-accessibility-function-yeast-1", "reader_count"=>58, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>13, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>1, "Student > Master"=>6, "Other"=>2, "Student > Bachelor"=>8, "Professor"=>7}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>13, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>1, "Student > Master"=>6, "Other"=>2, "Student > Bachelor"=>8, "Professor"=>7}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>13, "Agricultural and Biological Sciences"=>42, "Medicine and Dentistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>42}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>13}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Austria"=>1, "South Korea"=>1, "Sweden"=>1, "United States"=>4, "Philippines"=>1, "Germany"=>1, "Spain"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1579543"], "description"=>"<p>A. Scatterplots of relative chromatin accessibility between <i>S. cerevisiae</i> strains DBVPG1373 and UWOPS05_217_3 (top), <i>S. cerevisiae</i> strain UWOPS05_217_3 and <i>S. paradoxus</i> strain CBS432 (middle), and <i>S. cerevisiae</i> strain DBVPG1373 and <i>S. paradoxus</i> strain CBS432 (bottom). Note, comparisons within and between species are shown as blue and light green, respectively. B. Heatmap representation of chromatin accessibility at all NFRs in <i>S. cerevisiae</i> strain UWOPS05_217_3 versus <i>S. paradoxus</i> strain CBS432. Each row is a NFR, and columns are the two biological replicates of <i>S. cerevisiae</i> strain UWOPS05_217_3 and <i>S. paradoxus</i> strain CBS432. Rows are sorted by average difference in signal at NFRs between <i>S. cerevisiae</i> and <i>S. paradoxus</i>. The far right column indicates if the difference in chromatin accessibility between species is significant (yellow rectangles).</p>", "links"=>[], "tags"=>["Computational biology", "Comparative genomics", "Genome evolution", "Evolutionary biology", "genetics", "gene expression", "genomics", "chromatin", "accessibility"], "article_id"=>1092908, "categories"=>["Biological Sciences"], "users"=>["Caitlin F. Connelly", "Jon Wakefield", "Joshua M. Akey"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004427.g001", "stats"=>{"downloads"=>2, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Patterns_of_chromatin_accessibility_within_and_between_S_cerevisiae_and_S_paradoxus_/1092908", "title"=>"Patterns of chromatin accessibility within and between <i>S. cerevisiae</i> and <i>S. paradoxus</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-03 02:56:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/1579556"], "description"=>"<p>A. The odds ratio of observing a disrupted motif compared to a non-disrupted motif in NFRs with a significant <i>cis</i> effect. Odds ratios are shown for all motifs, as well as the two individual motifs (<i>GCN4</i> and <i>GZF3</i>) that were found to be significant by permutations (FDR = 0.10). B. Pattern of accessibility for four motifs found within <i>trans</i> effect NFRs that vary between <i>S. cerevisiae</i> and <i>S. paradoxus</i>.</p>", "links"=>[], "tags"=>["Computational biology", "Comparative genomics", "Genome evolution", "Evolutionary biology", "genetics", "gene expression", "genomics", "contributing"], "article_id"=>1092917, "categories"=>["Biological Sciences"], "users"=>["Caitlin F. Connelly", "Jon Wakefield", "Joshua M. Akey"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004427.g004", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Motifs_contributing_to_cis_and_trans_effects_/1092917", "title"=>"Motifs contributing to <i>cis</i> and <i>trans</i> effects.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-03 02:56:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/1579552"], "description"=>"<p>Top, an example of a NFR showing only a <i>trans</i> effect on chromatin accessibility. A <i>trans</i> effect is detected as a case where there is a difference in chromatin accessibility between the two parental haploid species, but there is no difference in chromatin accessibility between the two alleles in the hybrid. As shown above, this could be explained by a case where a nucleosome remodeler (shown as a hexagon) acts to evict nucleosomes and increase accessibility in <i>S. cerevisiae</i>, but a mutation in <i>S. paradoxus</i> has rendered it inactive and it is unable to evict the nucleosomes. In the diploid hybrid, the chromatin remodeler from <i>S. cerevisiae</i> is able to evict nucleosomes from both the <i>S. cerevisiae</i> and <i>S. paradoxus</i> chromosomes. Bottom, an example of a NFR showing only a <i>cis</i> effect on chromatin accessibility. A <i>cis</i> effect is detected as a difference between the accessibility detected between the two alleles in the diploid, and the lack of a <i>trans</i> effect is shown by the same difference being detected between the parental species. In this case, there has been a mutation at the NFR on the <i>S. cerevisiae</i> allele, leading to a difference in the number of nucleosomes binding in the region.</p>", "links"=>[], "tags"=>["Computational biology", "Comparative genomics", "Genome evolution", "Evolutionary biology", "genetics", "gene expression", "genomics", "chromatin"], "article_id"=>1092913, "categories"=>["Biological Sciences"], "users"=>["Caitlin F. Connelly", "Jon Wakefield", "Joshua M. Akey"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004427.g002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_of_approach_to_detect_cis_and_trans_effects_on_chromatin_accessibility_/1092913", "title"=>"Schematic of approach to detect <i>cis</i> and <i>trans</i> effects on chromatin accessibility.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-03 02:56:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/1579564"], "description"=>"<p>A. Boxplot of log<sub>2</sub>(effect size) of both <i>cis</i> and <i>trans</i> effects for FAIRE (dark grey) and RNA (light grey). B. Barplot of the percentage of genes with significant <i>cis</i> effects in RNA that are downstream of NFRs with and without <i>cis</i> effects (left). Barplot of the percentage of genes with significant <i>trans</i> effects in RNA that are downstream of NFRs with and without <i>trans</i> effects (right). C. Scatterplot of the log<sub>2</sub>(absolute value of the difference in chromatin accessibility between the two species) vs log<sub>2</sub>(absolute value of the difference in expression between the two species. The red dot indicates data from the <i>MET10</i> gene, whose FAIRE-Seq and RNA data are shown in panel D. For clarity, the FAIRE-Seq data is only shown in a 100 bp window on either side of the NFR. FAIRE signal is shown in black, and RNA signal is shown in grey.</p>", "links"=>[], "tags"=>["Computational biology", "Comparative genomics", "Genome evolution", "Evolutionary biology", "genetics", "gene expression", "genomics", "chromatin"], "article_id"=>1092925, "categories"=>["Biological Sciences"], "users"=>["Caitlin F. Connelly", "Jon Wakefield", "Joshua M. Akey"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004427.g005", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_expression_and_chromatin_accessibility_/1092925", "title"=>"Gene expression and chromatin accessibility.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-03 02:56:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/1579554"], "description"=>"<p>A. For each NFR, the relative chromatin accessibility in the haploid is plotted versus the relative chromatin accessibility in the diploid. NFRs with a significant <i>cis</i> effect are shown in pink. B. Reproduction of the plot from (A), but NFRs with a significant <i>trans</i> effect are shown in green. C. Violin plot showing the effect size distribution of <i>cis</i> and <i>trans</i> effects. D. Scatter plot of relative <i>cis</i> and <i>trans</i> effect sizes. Positive effects indicate higher accessibility in <i>S. cerevisiae</i> and negative effects indicate higher accessibility in <i>S. paradoxus</i>.</p>", "links"=>[], "tags"=>["Computational biology", "Comparative genomics", "Genome evolution", "Evolutionary biology", "genetics", "gene expression", "genomics", "chromatin"], "article_id"=>1092915, "categories"=>["Biological Sciences"], "users"=>["Caitlin F. Connelly", "Jon Wakefield", "Joshua M. Akey"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004427.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cis_and_trans_effects_on_chromatin_accessibility_/1092915", "title"=>"<i>Cis</i> and <i>trans</i> effects on chromatin accessibility.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-03 02:56:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/1579568", "https://ndownloader.figshare.com/files/1579569", "https://ndownloader.figshare.com/files/1579570"], "description"=>"<div><p>Chromatin accessibility is an important functional genomics phenotype that influences transcription factor binding and gene expression. Genome-scale technologies allow chromatin accessibility to be mapped with high-resolution, facilitating detailed analyses into the genetic architecture and evolution of chromatin structure within and between species. We performed Formaldehyde-Assisted Isolation of Regulatory Elements sequencing (FAIRE-Seq) to map chromatin accessibility in two parental haploid yeast species, <i>Saccharomyces cerevisiae</i> and <i>Saccharomyces paradoxus</i> and their diploid hybrid. We show that although broad-scale characteristics of the chromatin landscape are well conserved between these species, accessibility is significantly different for 947 regions upstream of genes that are enriched for GO terms such as intracellular transport and protein localization exhibit. We also develop new statistical methods to investigate the genetic architecture of variation in chromatin accessibility between species, and find that <i>cis</i> effects are more common and of greater magnitude than <i>trans</i> effects. Interestingly, we find that <i>cis</i> and <i>trans</i> effects at individual genes are often negatively correlated, suggesting widespread compensatory evolution to stabilize levels of chromatin accessibility. Finally, we demonstrate that the relationship between chromatin accessibility and gene expression levels is complex, and a significant proportion of differences in chromatin accessibility might be functionally benign.</p></div>", "links"=>[], "tags"=>["Computational biology", "Comparative genomics", "Genome evolution", "Evolutionary biology", "genetics", "gene expression", "genomics", "chromatin", "accessibility"], "article_id"=>1092929, "categories"=>["Biological Sciences"], "users"=>["Caitlin F. Connelly", "Jon Wakefield", "Joshua M. Akey"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1004427.s001", "https://dx.doi.org/10.1371/journal.pgen.1004427.s002", "https://dx.doi.org/10.1371/journal.pgen.1004427.s003"], "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evolution_and_Genetic_Architecture_of_Chromatin_Accessibility_and_Function_in_Yeast_/1092929", "title"=>"Evolution and Genetic Architecture of Chromatin Accessibility and Function in Yeast", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-07-03 02:56:18"}

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Relative Metric

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