@article{TEXTUAL,
      recid = {10582},
      author = {Candia, Paola de and Blekhman, Ran and Chabot, Adrien E.  and Oshlack, Alicia and Gilad, Yoav},
      title = {A Combination of Genomic Approaches Reveals the Role of  &amp;lt;i&amp;gt;FOXO1a&amp;lt;/i&amp;gt; in Regulating an Oxidative Stress  Response Pathway},
      journal = {PLOS ONE},
      address = {2008-02-27},
      number = {TEXTUAL},
      abstract = {&lt;p&gt;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, &lt;em&gt;FOXO1a&lt;/em&gt;, 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.&lt;/p&gt;&lt;p&gt;Methodology: 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  &lt;em&gt;FOXO1a&lt;/em&gt;. This set includes the gene for  thioredoxin-interacting protein (&lt;em&gt;TXNIP&lt;/em&gt;), the  expression of which is directly repressed by  &lt;em&gt;FOXO1a&lt;/em&gt;. The thioredoxin-interacting protein is  known to inhibit the reducing activity of thioredoxin  (&lt;em&gt;TRX&lt;/em&gt;), thereby hindering the cellular response to  oxidative stress and affecting life  span.&lt;/p&gt;&lt;p&gt;Conclusions: Our results provide an explanation  for the repeated observations that differences in the  regulation of &lt;em&gt;FOXO&lt;/em&gt; transcription factors affect  longevity. Moreover, we found that &lt;em&gt;TXNIP&lt;/em&gt; is  down-regulated in human compared to chimpanzee, consistent  with the up-regulation of its direct repressor  &lt;em&gt;FOXO1a&lt;/em&gt; in humans, and with differences in  longevity between the two species.&lt;/p&gt;},
      url = {http://knowledge.uchicago.edu/record/10582},
}