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| Status |
Public on May 10, 2021 |
| Title |
Foxp3 enhancers synergize to maximize regulatory T cell suppressive capacity [Cut&Run] |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| 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 |
CUT&RUN sequencing was used to assess the histone modifications (H3K4me3 and H3K27ac) and RNA polymerase II (Pol II) distribution around the Foxp3 locus in regulatory T cells of wild-type and Foxp3 enhancer deficiencies.
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| Contributor(s) |
He M, Zong X, Xu B, Feng Y |
| Citation(s) |
34086055 |
| |
| Submission date |
Sep 17, 2020 |
| Last update date |
Aug 09, 2021 |
| Contact name |
Beisi Xu |
| E-mail(s) |
beisi.xu@stjude.org
|
| Organization name |
St Jude Children's Research Hosipital
|
| Department |
Center for Applied Bioinformatics
|
| Street address |
262 Danny Thomas Pl
|
| 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 (12)
|
| GSM4792276 |
H3K4me3-CutRun-regulatory T cells-WT Foxp3-GFP |
| GSM4792277 |
H3K4me3-CutRun-regulatory T cells-Foxp3 CNS2 knockout |
| GSM4792278 |
H3K4me3-CutRun-regulatory T cells-Foxp3 CNS0 knockout |
| GSM4792279 |
H3K4me3-CutRun-regulatory T cells-Foxp3 CNS0 and CNS2 double knockout (CNS02DKO) |
| GSM4792280 |
H3K27ac-CutRun-regulatory T cells-WT Foxp3-GFP |
| GSM4792281 |
H3K27ac-CutRun-regulatory T cells-Foxp3 CNS2 knockout |
| GSM4792282 |
H3K27ac-CutRun-regulatory T cells-Foxp3 CNS0 knockout |
| GSM4792283 |
H3K27ac-CutRun-regulatory T cells-Foxp3 CNS0 and CNS2 double knockout (CNS02DKO) |
| GSM4792284 |
RNA Pol II-CutRun-regulatory T cells-WT Foxp3-GFP |
| GSM4792285 |
RNA Pol II-CutRun-regulatory T cells-Foxp3 CNS2 knockout |
| GSM4792286 |
RNA Pol II-CutRun-regulatory T cells-Foxp3 CNS0 knockout |
| GSM4792287 |
RNA Pol II-CutRun-regulatory T cells-Foxp3 CNS0 and CNS2 double knockout (CNS02DKO) |
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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 |
PRJNA664021 |
| SRA |
SRP282814 |
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