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Series GSE49667 Query DataSets for GSE49667
Status Public on Sep 09, 2013
Title DNA methylation differences between human regulatory T cells and conventional T cells
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary Regulatory T cells (Treg) prevent the emergence of autoimmune disease. Prototypic natural Treg (nTreg) are programmed by Forkhead-box P3 (FOXP3) and can be reliably identified by demethylation at the FOXP3 locus. To explore the nTreg methylation landscape we performed genome-wide methylation studies on human naïve resting nTreg (rTreg) and conventional naïve CD4+ T cells (Naïve). We detected 2,315 differentially methylated CpGs between these two cell types, many of which clustered into 127 regions of differential methylation (RDMs). T cell activation induced changes in 466 individual CpGs and 18 RDMs in naïve CD4+ T cells, but did not alter DNA methylation in rTreg. Expression of mRNA for TIGIT, an immune suppressive receptor demethylated in rTreg, was upregulated in nTreg and reduced in peripheral blood mononuclear cells of individuals at risk for autoimmune (type 1) diabetes. Gene-set testing of the 127 RDMs revealed enrichment of common Treg signature genes, FOXP3 bound genes and genes directly upregulated by FOXP3, which was primarily driven by the subset of demethylated RDMs. A putative Forkhead-binding motif overrepresented in promoter-associated RDMs suggests methylation regulates gene expression by influencing FOXP3 binding. Our findings provide new insights into epigenetic regulation of human nTreg and the potential to exploit differential methylation as an immune biomarker in human diseases.
Overall design Naïve and rTreg cells were sorted from buffy coats of 3 healthy male donors (M28, 29, 30) and then activated for 6 days with anti-CD3 and anti-CD28 antibodies, supplemented with IL-2 at day 4. DNA was harvested and bisulfite converted for methylation analysis on illumina HM450 array from 2-3 biological replicates of each cell type: rTreg (M28, M30), naïve (M28, M29, M30), Act-naïve (M28, M29, M30) and Act-rTreg (M29, M30).
Contributor(s) Zhang Y, Maksimovic J, Naselli G, Qian J, Blewitt ME, Oshlack A, Harrison LC, Chopin M
Citation(s) 23974203
Submission date Aug 08, 2013
Last update date Mar 22, 2019
Contact name Jovana Maksimovic
Organization name Murdoch Childrens Research Institute
Street address Royal Children's Hospital, Flemington Road
City Parkville
State/province Victoria
ZIP/Postal code 3052
Country Australia
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (10)
GSM1204705 naïve_rep1
GSM1204706 rTreg_rep1
GSM1204707 act_naive_rep1
BioProject PRJNA214687

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE49667_RAW.tar 183.1 Mb (http)(custom) TAR
GSE49667_signal_intensities.txt.gz 23.6 Mb (ftp)(http) TXT
Processed data included within Sample table

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