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| Status |
Public on Feb 09, 2015 |
| Title |
The chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Regulatory T cells (Tregs) are essential for maintaining proper immune homeostasis. Extracellular signals (e.g. TCR, CD28, IL-2R) are necessary for the generation and maintenance of Tregs, but how these signals are integrated to control the gene expression patterns of Tregs is less clear. Here we show that the epigenetic regulator, Ezh2, was induced by CD28 costimulation and Ezh2 activity was elevated in Tregs as compared to conventional CD4+ T cells. Deletion of Ezh2 in mouse Tregs led to a progressive autoimmune disease because Tregs were compromised after activation, losing proper control of essential Treg lineage genes and adopting a gene expression pattern similar to Foxp3-deficient ‘Tregs.’ Lineage-tracing of Ezh2-deficient Tregs in vivo confirmed that the cells were destabilized selectively in activated Treg populations, which led to a significant loss of Tregs in non-lymphoid tissues. These studies reveal an essential role for Ezh2 in the maintenance of Treg “identity” during cellular activation and differentiation.
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| Overall design |
RNAseq of sorted populations of CD62Lhi or CD62Llo Tregs for both Ezh2-HET (Foxp3YFP-Cre/Foxp3WT;Ezh2fl/+ female mice) and Ezh2-KO (Foxp3YFP-Cre/Foxp3WT;Ezh2fl/fl female mice) were generated, in triplicate for each condition, using Illumina HiSeq 2500 single-end 50bp sequencing platform.
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| Contributor(s) |
Chopra G, DuPage M, Bluestone JA |
| Citation(s) |
25680271 |
| |
| Submission date |
Jul 01, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
GAURAV CHOPRA |
| E-mail(s) |
gchopra@diabetes.ucsf.edu
|
| Organization name |
UNIVERSITY OF CALIFORNIA - SAN FRANCISCO (UCSF)
|
| Department |
DIABETES CENTER
|
| Lab |
BLUESTONE LAB
|
| Street address |
513 PARNASSUS AVE, HSW 1102
|
| City |
SAN FRANCISCO |
| State/province |
CA |
| ZIP/Postal code |
94109 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA254138 |
| SRA |
SRP044008 |
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