Dataset Information

A combination of genomic approaches reveals the role of FOXO1a in regulating an oxidative stress response pathway.

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.

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 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.

Conclusions

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.

SUBMITTER: de Candia P

PROVIDER: S-EPMC2244703 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Publications

A combination of genomic approaches reveals the role of FOXO1a in regulating an oxidative stress response pathway.

de Candia Paola P Blekhman Ran R Chabot Adrien E AE Oshlack Alicia A Gilad Yoav Y

PloS one 20080227 2

<h4>Background</h4>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 concentr ...[more]

PMID: 18301748

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Dataset Information

A combination of genomic approaches reveals the role of FOXO1a in regulating an oxidative stress response pathway.

Background

Methodology

Conclusions

Publications

A combination of genomic approaches reveals the role of FOXO1a in regulating an oxidative stress response pathway.

Similar Datasets

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