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| Status |
Public on May 10, 2021 |
| Title |
Foxp3 enhancers synergize to maximize regulatory T cell suppressive capacity [Bisulfite-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Treg cells bearing a diverse antigen receptor repertoire suppress pathogenic T cells and maintain immune homeostasis during their long lifespan. How their robust function is determined genetically remains elusive. Here, we investigate the regulatory space of the cis-regulatory elements of Treg lineage–specifying factor Foxp3. Foxp3 enhancers are known as distinct readers for environmental cues in promoting Treg cell induction or lineage stability. However, their single deficiencies cause mild, if any, immune dysregulation, leaving the key transcriptional mechanisms determining Foxp3 expression and thereby Treg suppressive capacity uncertain. We examined the collective activities of Foxp3 enhancers and found that they coordinate to maximize Treg cell induction, Foxp3 expression level, or lineage stability through distinct modes and that ablation of synergistic enhancers led to lethal autoimmunity in young mice. Thus, the induction and maintenance of a diverse, stable Treg cell repertoire rely on combinatorial Foxp3 enhancers, suggesting broad, stage-specific, synergistic activities of cell-intrinsic factors and -extrinsic cues in determining Treg suppressive capacity.
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| Overall design |
Genome-wide bisulfite sequencing (40x coverage) was performed with regulatory T cells isolated from mixed bone marrow chimeric mice generated with bone marrows from male donors of CD45.1 wild-type mice and CD45.2 mice of indicated genotypes to reveal the effect of Foxp3 enhancer deficiencies on local DNA methylation status.
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| Contributor(s) |
Fan Y, Xu B, Zong X, Feng Y |
| Citation(s) |
34086055 |
| |
| Submission date |
Sep 18, 2020 |
| Last update date |
Aug 09, 2021 |
| Contact name |
Beisi Xu |
| E-mail(s) |
beisi.xu@stjude.org
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| Organization name |
St Jude Children's Research Hosipital
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| Department |
Center for Applied Bioinformatics
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| Street address |
262 Danny Thomas Pl
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| City |
Memphis |
| State/province |
Tennessee |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| GSM4795512 |
WGBS-regulatory T cells-wild type Foxp3-GFP-replicate 1 |
| GSM4795513 |
WGBS-regulatory T cells-wild type Foxp3-GFP-replicate 2 |
| GSM4795514 |
WGBS-regulatory T cells- Foxp3 enhancer CNS2 knockout-replicate 1 |
| GSM4795515 |
WGBS-regulatory T cells- Foxp3 enhancer CNS2 knockout-replicate 2 |
| GSM4795516 |
WGBS-regulatory T cells- Foxp3 enhancer CNS0 knockout-replicate 1 |
| GSM4795517 |
WGBS-regulatory T cells- Foxp3 enhancer CNS0 knockout-replicate 2 |
| GSM4795518 |
WGBS-regulatory T cells- Foxp3 enhancer CNS0 and CNS2 double knockout-replicate 1 |
| GSM4795519 |
WGBS-regulatory T cells- Foxp3 enhancer CNS0 and CNS2 double knockout-replicate 2 |
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| This SubSeries is part of SuperSeries: |
| GSE158223 |
Foxp3 enhancers synergize to maximize regulatory T cell suppressive capacity |
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| Relations |
| BioProject |
PRJNA664383 |
| SRA |
SRP283863 |
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