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Series GSE40656 Query DataSets for GSE40656
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
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.
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.
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
Department Bioinformatics
Street address 101 Avenue of the Americas
City New York
State/province NY
ZIP/Postal code 10013
Country USA
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (4)
GSM998924 nTreg_Foxo1_Ab_ChIPseq
GSM998925 nTreg_Foxo1_Biotin_ChIPseq
GSM998926 nTreg_Input_Ab_ChIPseq
This SubSeries is part of SuperSeries:
GSE40657 Novel Foxo1-dependent Transcriptional Programs Control Treg Cell Function
SRA SRP015440
BioProject PRJNA174586

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Supplementary file Size Download File type/resource
GSE40656_RAW.tar 1.0 Mb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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