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Series GSE158222 Query DataSets for GSE158222
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
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.
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.
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
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
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
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
This SubSeries is part of SuperSeries:
GSE158223 Foxp3 enhancers synergize to maximize regulatory T cell suppressive capacity
BioProject PRJNA664383
SRA SRP283863

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Supplementary file Size Download File type/resource
GSE158222_RAW.tar 1.7 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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