Time-Dependent c-Myc Transactomes Mapped by Array-Based Nuclear Run-On Reveal Transcriptional Modules in Human B Cells
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{"title"=>"Time-dependent c-Myc transactomes mapped by array-based nuclear run-on reveal transcriptional modules in human B cells", "type"=>"journal", "authors"=>[{"first_name"=>"JinShui S.", "last_name"=>"Fan", "scopus_author_id"=>"7402794717"}, {"first_name"=>"Karen", "last_name"=>"Zeller", "scopus_author_id"=>"7005882625"}, {"first_name"=>"Yu Chi", "last_name"=>"Chen", "scopus_author_id"=>"37001730700"}, {"first_name"=>"Tonya", "last_name"=>"Watkins", "scopus_author_id"=>"7007002558"}, {"first_name"=>"Kathleen C.", "last_name"=>"Barnes", "scopus_author_id"=>"35394504000"}, {"first_name"=>"Kevin G.", "last_name"=>"Becker", "scopus_author_id"=>"35377219400"}, {"first_name"=>"Chi V.", "last_name"=>"Dang", "scopus_author_id"=>"7102119424"}, {"first_name"=>"Chris", "last_name"=>"Cheadle", "scopus_author_id"=>"6603422519"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"368277789", "sgr"=>"79551675788", "issn"=>"19326203", "pmid"=>"20300622", "scopus"=>"2-s2.0-79551675788", "doi"=>"10.1371/journal.pone.0009691", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"6f27fa27-0cfe-3168-8b41-2f5b6beb60e3", "abstract"=>"BACKGROUND: The definition of transcriptional networks through measurements of changes in gene expression profiles and mapping of transcription factor binding sites is limited by the moderate overlap between binding and gene expression changes and the inability to directly measure global nuclear transcription (coined \"transactome\"). METHODOLOGY/PRINCIPAL FINDINGS: We developed a method to measure nascent nuclear gene transcription with an Array-based Nuclear Run-On (ANRO) assay using commercial microarray platforms. This strategy provides the missing component, the transactome, to fully map transcriptional networks. ANRO measurements in an inducible c-Myc expressing human P493-6 B cell model reveals time-dependent waves of transcription, with a transactome early after c-Myc induction that does not persist at a late, steady-state phase, when genes that are regulated by c-Myc and E2F predominate. Gene set matrix analysis further uncovers functionally related groups of genes putatively regulated by waves of transcription factor motifs following Myc induction, starting with AP1 and CREB that are followed by EGR1, NFkB and STAT, and ending with E2F, Myc and ARNT/HIF motifs. CONCLUSIONS/SIGNIFICANCE: By coupling ANRO with previous global mapping of c-Myc binding sites by chromatin immunoprecipitation (ChIP) in P493-6 cells, we define a set of transcriptionally regulated direct c-Myc target genes and pave the way for the use of ANRO to comprehensively map any transcriptional network.", "link"=>"http://www.mendeley.com/research/timedependent-cmyc-transactomes-mapped-arraybased-nuclear-runon-reveal-transcriptional-modules-human", "reader_count"=>41, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>5, "Researcher"=>15, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>11, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>5, "Researcher"=>15, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>11, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>8, "Agricultural and Biological Sciences"=>27, "Medicine and Dentistry"=>3, "Chemistry"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>27}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>3, "Germany"=>2}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/858962"], "description"=>"<p>Enrichment values are sorted by their first appearance as upregulated in the NRO RNA. Identical analyses were run for both NRO and total RNA as indicated. Inset highlights genesets up-regulated at 48 hr.</p>", "links"=>[], "tags"=>["geneset", "changes", "transcription", "binding", "sites"], "article_id"=>529409, "categories"=>["Genetics", "Biochemistry", "Cancer", "Molecular Biology"], "users"=>["Jinshui Fan", "Karen Zeller", "Yu-Chi Chen", "Tonya Watkins", "Kathleen C. Barnes", "Kevin G. Becker", "Chi V. Dang", "Chris Cheadle"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009691.g006", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GSMA_geneset_analysis_of_coordinate_changes_in_gene_expression_based_on_the_presence_of_transcription_factor_binding_sites_in_selected_gene_lists_/529409", "title"=>"GSMA geneset analysis of coordinate changes in gene expression based on the presence of transcription factor binding sites in selected gene lists.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-15 02:36:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/426850", "https://ndownloader.figshare.com/files/426890", "https://ndownloader.figshare.com/files/426928", "https://ndownloader.figshare.com/files/427031", "https://ndownloader.figshare.com/files/427127", "https://ndownloader.figshare.com/files/427208"], "description"=>"<div><h3>Background</h3><p>The definition of transcriptional networks through measurements of changes in gene expression profiles and mapping of transcription factor binding sites is limited by the moderate overlap between binding and gene expression changes and the inability to directly measure global nuclear transcription (coined “transactome”).</p><h3>Methodology/Principal Findings</h3><p>We developed a method to measure nascent nuclear gene transcription with an Array-based Nuclear Run-On (ANRO) assay using commercial microarray platforms. This strategy provides the missing component, the transactome, to fully map transcriptional networks. ANRO measurements in an inducible c-Myc expressing human P493-6 B cell model reveals time-dependent waves of transcription, with a transactome early after c-Myc induction that does not persist at a late, steady-state phase, when genes that are regulated by c-Myc and E2F predominate. Gene set matrix analysis further uncovers functionally related groups of genes putatively regulated by waves of transcription factor motifs following Myc induction, starting with AP1 and CREB that are followed by EGR1, NFkB and STAT, and ending with E2F, Myc and ARNT/HIF motifs.</p><h3>Conclusions/Significance</h3><p>By coupling ANRO with previous global mapping of c-Myc binding sites by chromatin immunoprecipitation (ChIP) in P493-6 cells, we define a set of transcriptionally regulated direct c-Myc target genes and pave the way for the use of ANRO to comprehensively map any transcriptional network.</p></div>", "links"=>[], "tags"=>["time-dependent", "c-myc", "transactomes", "mapped", "array-based", "run-on", "transcriptional", "modules", "cells"], "article_id"=>144258, "categories"=>["Genetics", "Biochemistry", "Cancer", "Molecular Biology"], "users"=>["Jinshui Fan", "Karen Zeller", "Yu-Chi Chen", "Tonya Watkins", "Kathleen C. Barnes", "Kevin G. Becker", "Chi V. Dang", "Chris Cheadle"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0009691.s001", "https://dx.doi.org/10.1371/journal.pone.0009691.s002", "https://dx.doi.org/10.1371/journal.pone.0009691.s003", "https://dx.doi.org/10.1371/journal.pone.0009691.s004", "https://dx.doi.org/10.1371/journal.pone.0009691.s005", "https://dx.doi.org/10.1371/journal.pone.0009691.s006"], "stats"=>{"downloads"=>58, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Time_Dependent_c_Myc_Transactomes_Mapped_by_Array_Based_Nuclear_Run_On_Reveal_Transcriptional_Modules_in_Human_B_Cells/144258", "title"=>"Time-Dependent c-Myc Transactomes Mapped by Array-Based Nuclear Run-On Reveal Transcriptional Modules in Human B Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-03-15 01:10:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/858484"], "description"=>"<p>(<b>a, b</b>) Transcriptional regulation of CD69 in NRO RNA following Jurkat T Cell activation. (<b>a</b>) Illumina microarray - CD69 average signal intensity for 4 independent experiments. (<b>b</b>) CD 69 Real time PCR validation for the same experiments (fold changes were normalized by GAPDH controls). (<b>c, d</b>) RT-PCR estimates of varying amplicon size and complexity for CD69 gene transcription in PMA + I activated Jurkat T cell NRO RNA. (<b>c</b>) Fold changes for CD69 in NRO RNA were tested using either first strand cDNA or the final amplified cRNA product (as indicated). Multiple amplicons of GAPDH were similarly tested as an uninduced control. (<b>d</b>) CD69 amplicon primer design spans exon-intron genomic sequences of sizes as indicated (primer sequences are reported in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009691#s4\" target=\"_blank\">Materials and Methods</a>). Note the location of the Illumina microarray probe located at the 3′UTR.</p>", "links"=>[], "tags"=>["run-on"], "article_id"=>528938, "categories"=>["Genetics", "Biochemistry", "Cancer", "Molecular Biology"], "users"=>["Jinshui Fan", "Karen Zeller", "Yu-Chi Chen", "Tonya Watkins", "Kathleen C. Barnes", "Kevin G. Becker", "Chi V. Dang", "Chris Cheadle"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009691.g002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Array_based_Nuclear_Run_on_ANRO_characterization_/528938", "title"=>"Array- based Nuclear Run-on (ANRO) characterization.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-15 02:28:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/858849"], "description"=>"<p>Identical analyses were run for both NRO and total RNA as indicated. Examples of time-dependent up-regulated pathways at early, middle, and late time points.</p>", "links"=>[], "tags"=>["enrichment", "changes", "sorted", "upregulated", "nro"], "article_id"=>529298, "categories"=>["Genetics", "Biochemistry", "Cancer", "Molecular Biology"], "users"=>["Jinshui Fan", "Karen Zeller", "Yu-Chi Chen", "Tonya Watkins", "Kathleen C. Barnes", "Kevin G. Becker", "Chi V. Dang", "Chris Cheadle"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009691.g005", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pathway_enrichment_analysis_of_changes_in_gene_expression_sorted_by_their_first_appearance_as_upregulated_in_the_NRO_RNA_/529298", "title"=>"Pathway enrichment analysis of changes in gene expression sorted by their first appearance as upregulated in the NRO RNA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-15 02:34:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/859110"], "description"=>"<p>Fold changes are calculated between cells treated with tetracycline for 48 hrs versus untreated cells. Known MYC targets are as indicated (Y = yes).</p>", "links"=>[], "tags"=>["changes", "array-based", "nro", "rna", "illumina", "microarray"], "article_id"=>529559, "categories"=>["Genetics", "Biochemistry", "Cancer", "Molecular Biology"], "users"=>["Jinshui Fan", "Karen Zeller", "Yu-Chi Chen", "Tonya Watkins", "Kathleen C. Barnes", "Kevin G. Becker", "Chi V. Dang", "Chris Cheadle"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009691.t001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Selected_results_for_statistically_significant_changes_in_gene_expression_from_either_Array_based_NRO_or_total_RNA_as_measured_on_the_Illumina_microarray_platform_/529559", "title"=>"Selected results for statistically significant changes in gene expression from either Array-based NRO or total RNA as measured on the Illumina microarray platform.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-03-15 02:39:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/858601"], "description"=>"<p>(<b>a</b>) Pearson's Correlation Matrix of changes in gene expression (log ratios) between tet treated (T) and untreated (UT) P493-6 human B cells following 48 hr induction for a common pool of approximately 7800 genes as measured on both Illumina BeadArrays and Affymetrix Exon microarray platforms. (<b>b</b>) heat map illustrating a selection of the highest scoring pathways using Gene Set Matrix Analysis (GSMA) on the logratios from (<b>a</b>). (<b>c</b>) Pathway breakout from <b>b</b> on a gene by gene basis for the Inteferon a, b Response Genes. Log ratios sorted descending on the NRO as measured on the Illumina platform ((ILL T-UT NRO).</p>", "links"=>[], "tags"=>["run-on", "shows", "affymetrix", "exon", "arrays", "illumina"], "article_id"=>529050, "categories"=>["Genetics", "Biochemistry", "Cancer", "Molecular Biology"], "users"=>["Jinshui Fan", "Karen Zeller", "Yu-Chi Chen", "Tonya Watkins", "Kathleen C. Barnes", "Kevin G. Becker", "Chi V. Dang", "Chris Cheadle"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009691.g003", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Array_based_Nuclear_Run_on_ANRO_shows_consistent_results_between_Affymetrix_exon_arrays_and_Illumina_BeadChips_/529050", "title"=>"Array- based Nuclear Run-on (ANRO) shows consistent results between Affymetrix exon arrays and Illumina BeadChips.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-15 02:30:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/858373"], "description"=>"<p>(<b>a</b>) schematic for optimized ANRO protocol. (<b>b</b>) heat map of relative gene expression intensities for a panel of test genes activated by PMA+ionomycin induction of human Jurkat T cells. Increasing amounts of T7 random primer used in the first strand cDNA synthesis of Nuclear Run-on RNA accompanied by increasing amounts of the resulting cRNA generated and applied to Illumina microarrays show no increase in signal.</p>", "links"=>[], "tags"=>["run-on"], "article_id"=>528827, "categories"=>["Genetics", "Biochemistry", "Cancer", "Molecular Biology"], "users"=>["Jinshui Fan", "Karen Zeller", "Yu-Chi Chen", "Tonya Watkins", "Kathleen C. Barnes", "Kevin G. Becker", "Chi V. Dang", "Chris Cheadle"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009691.g001", "stats"=>{"downloads"=>2, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Array_based_Nuclear_Run_on_ANRO_development_and_optimization_/528827", "title"=>"Array- based Nuclear Run-on (ANRO) development and optimization.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-15 02:27:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/858699"], "description"=>"<p>At each time point, 6 independent experiments were performed, except for the 48 hr time point that has 10 experiments shown. Coordinate increase in gene expression for 970 genes is contrasted between nascent nuclear gene transcription (NRO RNA) and changes in gene expression at the whole cell level (Total RNA) at the timepoints indicated. Changes in gene expression are calculated as logratios relative to 0time. Inset shows all changes measured (10,530).</p>", "links"=>[], "tags"=>["p493-6", "cells", "myc"], "article_id"=>529150, "categories"=>["Genetics", "Biochemistry", "Cancer", "Molecular Biology"], "users"=>["Jinshui Fan", "Karen Zeller", "Yu-Chi Chen", "Tonya Watkins", "Kathleen C. Barnes", "Kevin G. Becker", "Chi V. Dang", "Chris Cheadle"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009691.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Heatmap_of_a_time_course_of_gene_regulation_in_human_P493_6_B_cells_following_Myc_gene_induction_/529150", "title"=>"Heatmap of a time course of gene regulation in human P493-6 B cells following Myc gene induction.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-15 02:32:30"}

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Relative Metric

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