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Series GSE169385 Query DataSets for GSE169385
Status Public on May 10, 2021
Title Foxp3 enhancers synergize to maximize regulatory T cell suppressive capacity [Capture-C]
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.
 
Overall design Capture-C was used to assess the three-dimensional chromatin architecture around the Foxp3 locus in Treg precursor cells (i.e., CD4 naïve T cells), ASC-treated iTreg cells, and natural Treg cells.
 
Contributor(s) Wright S, Li C, Xu B, Li J, Zong X, Feng Y
Citation(s) 34086055
Submission date Mar 22, 2021
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
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (10)
GSM5201391 Capture C_Tn-1 (CD4+GFP+CD62L+CD44- naive T cells sorted from male Foxp3-GFP mice)
GSM5201392 Capture C_Tn-2 (CD4+GFP+CD62L+CD44- naive T cells sorted from male Foxp3-GFP mice)
GSM5201393 Capture C_Tn-3 (CD4+GFP+CD62L+CD44- naive T cells sorted from male Foxp3-GFP mice)
This SubSeries is part of SuperSeries:
GSE158223 Foxp3 enhancers synergize to maximize regulatory T cell suppressive capacity
Relations
BioProject PRJNA716354
SRA SRP311708

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Supplementary file Size Download File type/resource
GSE169385_RAW.tar 4.3 Mb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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