A Combination of Genomic Approaches Reveals the Role of FOXO1a in Regulating an Oxidative Stress Response Pathway
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{"title"=>"A combination of genomic approaches reveals the role of FOXO1a in regulating an oxidative stress response pathway", "type"=>"journal", "authors"=>[{"first_name"=>"Paola", "last_name"=>"de Candia", "scopus_author_id"=>"6602511190"}, {"first_name"=>"Ran", "last_name"=>"Blekhman", "scopus_author_id"=>"11440262400"}, {"first_name"=>"Adrien E.", "last_name"=>"Chabot", "scopus_author_id"=>"16836022300"}, {"first_name"=>"Alicia", "last_name"=>"Oshlack", "scopus_author_id"=>"55882468700"}, {"first_name"=>"Yoav", "last_name"=>"Gilad", "scopus_author_id"=>"6602166624"}], "year"=>2008, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-45749107163", "sgr"=>"45749107163", "pui"=>"351865657", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "pmid"=>"18301748", "doi"=>"10.1371/journal.pone.0001670"}, "id"=>"ca87a233-d345-3827-9318-2a7be7814d88", "abstract"=>"BACKGROUND: While many of the phenotypic differences between human and chimpanzee may result from changes in gene regulation, only a handful of functionally important regulatory differences are currently known. As a first step towards identifying transcriptional pathways that have been remodeled in the human lineage, we focused on a transcription factor, FOXO1a, which we had previously found to be up-regulated in the human liver compared to that of three other primate species. We concentrated on this gene because of its known role in the regulation of metabolism and in longevity.\\n\\nMETHODOLOGY: Using a combination of expression profiling following siRNA knockdown and chromatin immunoprecipitation in a human liver cell line, we identified eight novel direct transcriptional targets of FOXO1a. This set includes the gene for thioredoxin-interacting protein (TXNIP), the expression of which is directly repressed by FOXO1a. The thioredoxin-interacting protein is known to inhibit the reducing activity of thioredoxin (TRX), thereby hindering the cellular response to oxidative stress and affecting life span.\\n\\nCONCLUSIONS: Our results provide an explanation for the repeated observations that differences in the regulation of FOXO transcription factors affect longevity. Moreover, we found that TXNIP is down-regulated in human compared to chimpanzee, consistent with the up-regulation of its direct repressor FOXO1a in humans, and with differences in longevity between the two species.", "link"=>"http://www.mendeley.com/research/combination-genomic-approaches-reveals-role-foxo1a-regulating-oxidative-stress-response-pathway", "reader_count"=>38, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>8, "Researcher"=>10, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>2, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>8, "Researcher"=>10, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>2, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>27, "Medicine and Dentistry"=>6, "Neuroscience"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>27}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>4, "Brazil"=>1, "Germany"=>1}, "group_count"=>1}

Scopus | Further Information

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  • {"files"=>["https://ndownloader.figshare.com/files/936211"], "description"=>"<p>Gel electrophoresis pictures of PCR amplifications following <i>FOXO1a</i> ChIP, for the putative promoters of the eight direct transcriptional targets of <i>FOXO1a</i>.</p>", "links"=>[], "tags"=>["evolutionary biology/evolutionary and comparative genetics", "genetics and genomics/comparative genomics", "evolutionary biology/human evolution"], "article_id"=>606654, "categories"=>["Evolutionary Biology", "Genetics"], "users"=>["Paola de Candia", "Ran Blekhman", "Adrien E. Chabot", "Alicia Oshlack", "Yoav Gilad"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001670.g002", "stats"=>{"downloads"=>5, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FOXO1a_ChIP_results_/606654", "title"=>"<i>FOXO1a</i> ChIP results.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-27 01:50:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/936310"], "description"=>"<p>Mean fold differences (y-axis) and standard errors for six biological replicates (different individuals) are given for either the human (dark bars) or chimpanzee (clear bars) liver RNA samples. For each gene (x-axis), results were standardized based on the species with the lower expression level (set to 1). Stars indicate gene that are differentially expressed between human and chimpanzee at either <i>P</i><0.1 (*) or <i>P</i><0.05 (**) (see text).</p>", "links"=>[], "tags"=>["rt-pcr"], "article_id"=>606755, "categories"=>["Evolutionary Biology", "Genetics"], "users"=>["Paola de Candia", "Ran Blekhman", "Adrien E. Chabot", "Alicia Oshlack", "Yoav Gilad"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001670.g003", "stats"=>{"downloads"=>3, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantitative_RT_PCR_results_/606755", "title"=>"Quantitative RT-PCR results.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-27 01:52:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/936386"], "description"=>"<p>Mean fold activity compared to the control empty vector (y-axis) and standard errors for five replicates are given for either the original <i>TXNIP</i> promoter (dark bars) or the mutated version (empty bars).</p>", "links"=>[], "tags"=>["assays"], "article_id"=>606836, "categories"=>["Evolutionary Biology", "Genetics"], "users"=>["Paola de Candia", "Ran Blekhman", "Adrien E. Chabot", "Alicia Oshlack", "Yoav Gilad"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001670.g004", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reporter_gene_assays_with_TXNIP_promoter_/606836", "title"=>"Reporter gene assays with <i>TXNIP</i> promoter.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-27 01:53:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/461401", "https://ndownloader.figshare.com/files/461457", "https://ndownloader.figshare.com/files/461493"], "description"=>"<div><h3>Background</h3><p>While many of the phenotypic differences between human and chimpanzee may result from changes in gene regulation, only a handful of functionally important regulatory differences are currently known. As a first step towards identifying transcriptional pathways that have been remodeled in the human lineage, we focused on a transcription factor, <em>FOXO1a</em>, which we had previously found to be up-regulated in the human liver compared to that of three other primate species. We concentrated on this gene because of its known role in the regulation of metabolism and in longevity.</p><h3>Methodology</h3><p>Using a combination of expression profiling following siRNA knockdown and chromatin immunoprecipitation in a human liver cell line, we identified eight novel direct transcriptional targets of <em>FOXO1a</em>. This set includes the gene for thioredoxin-interacting protein (<em>TXNIP</em>), the expression of which is directly repressed by <em>FOXO1a</em>. The thioredoxin-interacting protein is known to inhibit the reducing activity of thioredoxin (<em>TRX</em>), thereby hindering the cellular response to oxidative stress and affecting life span.</p><h3>Conclusions</h3><p>Our results provide an explanation for the repeated observations that differences in the regulation of <em>FOXO</em> transcription factors affect longevity. Moreover, we found that <em>TXNIP</em> is down-regulated in human compared to chimpanzee, consistent with the up-regulation of its direct repressor <em>FOXO1a</em> in humans, and with differences in longevity between the two species.</p></div>", "links"=>[], "tags"=>["genomic", "approaches", "reveals", "regulating", "oxidative", "pathway"], "article_id"=>150929, "categories"=>["Evolutionary Biology", "Genetics"], "users"=>["Paola de Candia", "Ran Blekhman", "Adrien E. Chabot", "Alicia Oshlack", "Yoav Gilad"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0001670.s001", "https://dx.doi.org/10.1371/journal.pone.0001670.s002", "https://dx.doi.org/10.1371/journal.pone.0001670.s003"], "stats"=>{"downloads"=>7, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Combination_of_Genomic_Approaches_Reveals_the_Role_of_FOXO1a_in_Regulating_an_Oxidative_Stress_Response_Pathway/150929", "title"=>"A Combination of Genomic Approaches Reveals the Role of <em>FOXO1a</em> in Regulating an Oxidative Stress Response Pathway", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2008-02-27 00:15:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/936099"], "description"=>"<p>A. <i>FOXO1a</i> Western blots are shown for one of the three siRNA biological replicates, indicating that the level of the FOXO1a protein is dramatically reduced. B. Zoom into a picture of a cDNA microarray co-hybridization of RNA from one biological replicate of cells treated with <i>FOXO1a</i> siRNA (Cy3 - green) and RNA from untreated cells (Cy5 - red). The circle marks the cDNA probe for <i>FOXO1a</i>. As can be seen, <i>FOXO1a</i> mRNA levels are reduced following the knockdown. We note that this microarray result was validated by using quantitative RT-PCR. C. A volcano plot for results of the comparison of gene expression profiles following <i>FOXO1a</i> knockdown to the control siRNA treatment. The eight confirmed direct transcriptional target of <i>FOXO1a</i> are indicated by arrows. In the plot, all <i>P</i>-values smaller than 10<sup>−9</sup> are plotted as <i>P</i> = 10<sup>−10</sup> (<i>P</i>-values ranged from 1 to 10<sup>−43</sup>).</p>", "links"=>[], "tags"=>["knockdown"], "article_id"=>606542, "categories"=>["Evolutionary Biology", "Genetics"], "users"=>["Paola de Candia", "Ran Blekhman", "Adrien E. Chabot", "Alicia Oshlack", "Yoav Gilad"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001670.g001", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FOXO1a_knockdown_in_human_HepG2_C3A_liver_cells_/606542", "title"=>"<i>FOXO1a</i> knockdown in human HepG2/C3A liver cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-27 01:49:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/936442"], "description"=>"<p>Potential direct transcriptional targets of <i>FOXO1a</i> identified <i>in-silico</i></p>", "links"=>[], "tags"=>["transcriptional", "targets"], "article_id"=>606890, "categories"=>["Evolutionary Biology", "Genetics"], "users"=>["Paola de Candia", "Ran Blekhman", "Adrien E. Chabot", "Alicia Oshlack", "Yoav Gilad"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001670.t001", "stats"=>{"downloads"=>6, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Potential_direct_transcriptional_targets_of_FOXO1a_identified_in_silico_/606890", "title"=>"Potential direct transcriptional targets of <i>FOXO1a</i> identified <i>in-silico</i>", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-02-27 01:54:50"}

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  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
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  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"2", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
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  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
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  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"6", "full-text"=>"3", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"14", "full-text"=>"12", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"18", "full-text"=>"19", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"2", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"3", "full-text"=>"1", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
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Relative Metric

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