biomedical and healthCAre Data Discovery Index Ecosystem
biomedical and healthCAre Data Discovery Index Ecosystem
| Title: | Novel Foxo1-dependent Transcriptional Programs Control Treg Cell Function [ChIP-Seq]
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| dateReleased: |
09-07-2012
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| description: |
Regulatory T (Treg) cells characterized by expression of the transcription factor forkhead box P3 (Foxp3) maintain immune homeostasis by suppressing self-destructive immune responses1-4. Foxp3 operates as a late acting differentiation factor controlling Treg cell homeostasis and function5, whereas the early Treg cell lineage commitment is regulated by the Akt kinase and the forkhead box O (Foxo) family of transcription factors6-10. However, whether Foxo proteins act beyond the Treg cell commitment stage to control Treg cell homeostasis and function remains largely unexplored. Here we show that Foxo1 is a pivotal regulator of Treg cell function. Treg cells express high amounts of Foxo1, and display reduced T-cell receptor-induced Akt activation, Foxo1 phosphorylation, and Foxo1 nuclear exclusion. Mice with Treg cell-specific deletion of Foxo1 develop a fatal inflammatory disorder similar in severity to Foxp3-deficient mice, but without the loss of Treg cells. Genome-wide analysis of Foxo1 binding sites reveals ~300 Foxo1-bound target genes, including the proinflammatory cytokine Ifng, that do not appear to be directly regulated by Foxp3. These findings demonstrate that the evolutionarily ancient Akt-Foxo1 signaling module controls a novel genetic program indispensable for Treg cell function. Treg cells were isolated from wild-type B6 mice or Foxo1tagBirA mice in which foxo1 is endogenously biotinylated. Foxo1 binding targets in Treg cells were identified by using Foxo1 antibody- and Streptavidin- ChIP-Seq approaches.
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| privacy: |
not applicable
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| aggregation: |
instance of dataset
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| ID: |
E-GEOD-40656
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| refinement: |
raw
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| alternateIdentifiers: |
40656
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| keywords: |
functional genomics
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| dateModified: |
05-02-2014
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| availability: |
available
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| types: |
gene expression
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| name: |
Mus musculus
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| accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-40656/E-GEOD-40656.raw.1.zip |
| storedIn: |
ArrayExpress
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| qualifier: |
gzip compressed
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| format: |
TXT
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| accessType: |
download
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| authentication: |
none
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| authorization: |
none
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| accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-40656/E-GEOD-40656.processed.1.zip |
| storedIn: |
ArrayExpress
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| qualifier: |
gzip compressed
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| format: |
TXT
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| accessType: |
download
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| authentication: |
none
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| authorization: |
none
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| accessURL: | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE40656 |
| storedIn: |
Gene Expression Omnibus
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| qualifier: |
not compressed
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| format: |
HTML
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| accessType: |
landing page
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| primary: |
true
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| authentication: |
none
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| authorization: |
none
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| abbreviation: |
EBI
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| homePage: | http://www.ebi.ac.uk/ |
| ID: |
SCR:004727
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| name: |
European Bioinformatics Institute
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| homePage: | https://www.ebi.ac.uk/arrayexpress/ |
| ID: |
SCR:002964
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| name: |
ArrayExpress
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