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Series GSE57272 Query DataSets for GSE57272
Status Public on Sep 04, 2014
Title Conserved non-coding sequence 2 (CNS2) of the Foxp3 genomic locus is essential for the function and stability of regulatory T cells during their activation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Regulatory T (Treg) cells play an indispensable role in immune homeostasis. The development and function of Tregs are dependent on transcriptional factor Foxp3, but how constant expression of Foxp3 is maintained in Tregs is not clear. Here we show that ablation of the conserved non-coding DNA sequence 2 (CNS2) at the Foxp3 locus in mice led to spontaneous lymphoproliferative disease and exacerbation of experimental autoimmune encephalomyelitis (EAE). CNS2 is required for activated Treg cells to maintain elevated Foxp3 expression, which is critical for their suppressor function and lineage stability. Mechanistically, upon TCR stimulation, NFAT binds to both CNS2 and Foxp3 promoter and mediates the interaction between CNS2 and Foxp3 promoter. Our findings demonstrated an essential role for CNS2 in maintaining the stability and function of activated Treg cells and identified NFAT as a key mediator of its function.
Overall design Gene expression was profiled in T regulatory cells (Treg) in WT and CNS2 knockout mice. CNS2 knockout mice lack a conserved non-coding DNA sequence 2 (CNS2) at the Foxp3 locus. Treg cells were further sorted into Foxp3-high and Foxp3-low populations based on the expression level of Foxp3. mRNA was profiled using RNA-Seq (unstranded, polyA+, SE100) in replicate for each condition
Contributor(s) Li X, Liang Y, LeBlanc M, Benner C, Zheng Y
Citation(s) 25126782
Submission date May 05, 2014
Last update date May 15, 2019
Contact name Christopher Benner
Organization name University of California, San Diego (UCSD)
Department Medicine
Street address 9500 Gilman Dr. MC 0640
City La Jolla
State/province California
ZIP/Postal code 92093-0640
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (8)
GSM1378168 Treg CNS2-/- Foxp3 high rep1
GSM1378169 Treg CNS2-/- Foxp3 low rep1
GSM1378170 Treg CNS2-/- Foxp3 high rep2
BioProject PRJNA246149
SRA SRP041655

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Supplementary file Size Download File type/resource
GSE57272_rpkm.txt.gz 2.3 Mb (ftp)(http) TXT
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