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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 12, 2014 |
| Title |
Two Histone/Protein Acetyltransferases, CBP and p300, Are Indispensable for Foxp3+ T-regulatory Cell Development and Function |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
T-regulatory (Treg) cells are important to immune homeostasis, and Treg cell deficiency or dysfunction leads to autoimmune disease. An histone/protein acetyltransferase (HAT), p300, was recently found important for Treg function and stability, but further insights into the mechanisms by which p300 or other HATs affect Treg biology are needed. Here we show that CBP, a p300 paralog, is also important in controlling Treg function and stability. Thus, while mice with Treg-specific deletion of CBP or p300 developed minimal autoimmune disease, the combined deletion of CBP and p300 led to fatal autoimmunity by 3-4 weeks of age. The effects of CBP and p300 deletion on Treg development are dose-dependent, and involve multiple mechanisms. CBP and p300 cooperate with several key Treg transcription factors that act on the Foxp3 promoter to promote Foxp3 production. CBP and p300 also act on the Foxp3 CNS2 region to maintain Treg stability in inflammatory environments by regulating pCREB function and GATA3 expression, respectively. Lastly, CBP and p300 regulate the epigenetic status and function of Foxp3. Our findings provide insights into how HATs orchestrate multiple aspects of Treg development and function, and identify overlapping but also discrete activities for p300 and CBP in control of Treg cells.
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| Overall design |
RNA from three independent samples from magnetically separated CD4+CD25+ Treg of fl-p300/Foxp3cre mice and fl-CBP/Foxp3cre, compared to wild type (Foxp3cre) control (all C57Bl/6 background).
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| Contributor(s) |
Liu Y, Wang L, Han R, Beier UH, Akimova T, Bhatti TR, Xiao H, Cole PA, Brindle PK, Hancock WW |
| Citation(s) |
25154413 |
| Submission date |
Aug 11, 2014 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Wayne W Hancock |
| Organization name |
CHOP/UPenn
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| Street address |
916B ARC, 3615 Civic Ctr Blvd
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104-4318 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA258019 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE60318_RAW.tar |
16.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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