|
| Status |
Public on Aug 23, 2012 |
| Title |
Gene expression profiling in Treg cells deficient or mutant in candidate FoxP3 cofactors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The transcription factor FoxP3 partakes dominantly in the specification and function of FoxP3+ CD4+ T regulatory cells (Tregs), but is neither strictly necessary nor sufficient to determine the characteristic Treg transcriptional signature. Computational network inference and experimental testing assessed the contribution of several other transcription factors (TFs). Enforced expression of Helios or Xbp1 elicited specific signatures, but Eos, Irf4, Satb1, Lef1 and Gata1 elicited exactly the same outcome, synergizing with FoxP3 to activate most of the Treg signature, including key TFs, and enhancing FoxP3 occupancy at its genomic targets. Conversely, the Treg signature was robust to inactivation of any single cofactor. A redundant genetic switch thus locks-in the Treg phenotype, a model which accounts for several aspects of Treg physiology, differentiation and stability.
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| Overall design |
To study the impact of deficiency of candidate FoxP3 cofactors (Xbp1, Eos, Gata1) on the expression of the Treg transcriptional signature, gene expression profiles were generated from purified splenic CD4+CD25hi Tregs of these mutant or knockout mice and their wildtype littermates.
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| |
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| Contributor(s) |
Hill J, Mathis D, Benoist C |
| Citation(s) |
22961053 |
| Submission date |
Aug 21, 2012 |
| Last update date |
Mar 04, 2019 |
| Contact name |
CBDM Lab |
| E-mail(s) |
cbdm@hms.harvard.edu
|
| Phone |
617-432-7747
|
| Organization name |
Harvard Medical School
|
| Department |
Microbiology and Immunobiology
|
| Lab |
CBDM
|
| Street address |
77 Avenue Louis Pasteur
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
|
| Samples (12)
|
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| This SubSeries is part of SuperSeries: |
| GSE40278 |
A multiply redundant genetic switch locks in the transcriptional signature of T regulatory cells |
|
| Relations |
| BioProject |
PRJNA173378 |
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