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| Status |
Public on Oct 04, 2012 |
| Title |
The Transcription Factor T-bet Is Induced by Multiple Pathways and Prevents an Endogenous Th2 Cell Program during Th1 Cell Responses |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
T-bet is a critical transcription factor for T helper 1 (Th1) cell differentiation. To study the regulation and functions of T-bet, we developed a T-bet-ZsGreen reporter mouse strain, in which GFP faithfully reflects the expression of T-bet. By using this tool, we report that signals elicited by IL-12 and IFNg are redundant in inducing T-bet in mice infected with Toxoplasma gondii and that T-bet does not contribute to its own expression when induced by IL-12 and IFNg. While both T-bet and Stat4 are critical for IFNg production, IFNg signaling is dispensable. Strikingly, loss of T-bet results in activation of an endogenous Th2 program in cells expressing T-bet-ZsGreen. Genome-wide analyses suggest T-bet directly induces Th1-related genes but indirectly suppresses Th2-related genes. Our study revealed redundancy and synergy among several Th1-inducing pathways in regulating the expression of T-bet and IFNg, and a critical role of T-bet in suppressing an endogenous Th2 program.
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| Overall design |
RNA-Seq experiments were performed using total RNAs isolated from both wild type and Tbx21-/- Th1 cells in duplicates. Tbet ChIP-seq was performed using wild type Th1 cells. H3K4me1 and H3K27me3 ChIP-seq was performed using both wild type and Tbx21-/- Th1 cells.
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| Contributor(s) |
Zhu J, Jankovic D, Oler AJ, Wei G, Sharma S, Hu G, Guo L, Yagi R, Yamane H, Punkosdy G, Feigenbaum L, Zhao K, Paul WE |
| Citation(s) |
23041064 |
| Submission date |
Jun 19, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Andrew J Oler |
| E-mail(s) |
andrew.oler@nih.gov
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| Organization name |
NIAID/NIH
|
| Department |
Bioinformatics and Computational Biosciences Branch (BCBB)
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| Lab |
Computational Biology Section
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| Street address |
31 Center Drive, Room 3B62E
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (2) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA168983 |
| SRA |
SRP013826 |
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