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| 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
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| 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.
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| 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).
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| 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
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| Street address |
Royal Children's Hospital, Flemington Road
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| City |
Parkville |
| State/province |
Victoria |
| ZIP/Postal code |
3052 |
| Country |
Australia |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA214687 |
| 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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