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| Status |
Public on Sep 07, 2012 |
| Title |
Novel Foxo1-dependent Transcriptional Programs Control Treg Cell Function [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
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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| Contributor(s) |
Ouyang W, Liao W, Luo C, Yin N, Huse M, Kim MV, Peng M, Chan P, Ma Q, Mo Y, Meijer D, Zhao K, Rudensky AY, Atwal G, Zhang MQ, Li MO |
| Citation(s) |
23135404 |
| Submission date |
Sep 06, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Willey Liao |
| Organization name |
New York Genome Center
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| Department |
Bioinformatics
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| Street address |
101 Avenue of the Americas
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10013 |
| Country |
USA |
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| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE40657 |
Novel Foxo1-dependent Transcriptional Programs Control Treg Cell Function |
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| Relations |
| SRA |
SRP015440 |
| BioProject |
PRJNA174586 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE40656_RAW.tar |
1.0 Mb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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