 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jan 08, 2010 |
| Title |
Analysis of interleukin-21-induced Prdm1 gene regulation reveals functional cooperation of STAT3 and IRF4 TFs |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Interleukin-21 (IL-21) is a pleiotropic cytokine that induces expression of transcription factor BLIMP1 (encoded by Prdm1), which regulates plasma cell differentiation and T cell homeostasis. We identified an IL-21 response element downstream of Prdm1 that binds the transcription factors STAT3 and IRF4, which are required for optimal Prdm1 expression. Genome-wide ChIP-Seq mapping of STAT3- and IRF4-binding sites showed that most regions with IL-21-induced STAT3 binding also bound IRF4 in vivo, and furthermore, revealed that the noncanonical TTCnnnTAA GAS motif critical in Prdm1 was broadly used for STAT3 binding. Comparing genome-wide expression array data to binding sites revealed that most IL-21-regulated genes were associated with combined STAT3-IRF4 sites rather than pure STAT3 sites. Correspondingly, ChIP-Seq analysis of Irf4_/_ T cells showed greatly diminished STAT3 binding after IL-21 treatment, and Irf4_/_ mice showed impaired IL- 21-induced Tfh cell differentiation in vivo. These results reveal broad cooperative gene regulation by STAT3 and IRF4.
|
| |
|
| Overall design |
Affymetrix expression data: Prepare CD4+ T cells from spleen. CD4+ T cells were preactivated, rested, and treated with IL-21 for 1, 6, and 24 hours.
ChIP-seq data: Profiling of IRF4 and Stat3 binding with and without IL-21 stimulation in wild type and IRF4 KO mice.
|
| |
|
| Contributor(s) |
Kwon H, Thierry-Mieg D, Thierry-Mieg J, Oh J, Leonard WJ |
| Citation(s) |
20064451 |
| |
| Submission date |
Nov 25, 2009 |
| Last update date |
May 15, 2019 |
| Contact name |
Warren J Leonard |
| E-mail(s) |
leonardw@nhlbi.nih.gov
|
| Phone |
301-496-0098
|
| Organization name |
NHLBI/NIH
|
| Lab |
MSC 1674
|
| Street address |
10 Center Dr
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
|
| Samples (56)
|
| GSM475960 |
S10SG_Ctrl_4 |
| GSM475961 |
S10SG_Ctrl_5 |
| GSM475962 |
S10SG-1h_1 |
| GSM475963 |
S10SG-1h_2 |
| GSM475964 |
S10SG-1h_3 |
| GSM475965 |
S10SG-1h_4 |
| GSM475966 |
S10SG-1h_5 |
| GSM475967 |
S10SG_6h_1 |
| GSM475968 |
S10SG_6h_2 |
| GSM475969 |
S10SG_6h_3 |
| GSM475970 |
S10SG_6h_4 |
| GSM475971 |
S10SG_6h_5 |
| GSM475972 |
S10SG_24h_1 |
| GSM475973 |
S10SG_24h_2 |
| GSM475974 |
S10SG_24h_3 |
| GSM475975 |
S10SG_24h_4 |
| GSM475976 |
S10SG_24h_5 |
| GSM494676 |
IRF4 bound pre IL21, seq 1 |
| GSM494677 |
IRF4 bound pre IL21, seq 2 |
| GSM494678 |
IRF4 bound pre IL21 dup, seq 1 |
| GSM494679 |
IRF4 bound pre IL21 dup, seq 2 |
| GSM494680 |
IRF4 bound post IL21, seq 1 |
| GSM494681 |
IRF4 bound post IL21, seq 2 |
| GSM494682 |
IRF4 bound post IL21 dup, seq 1 |
| GSM494683 |
IRF4 bound post IL21 dup, seq 2 |
| GSM494684 |
STAT3 bound pre IL21, seq 1 |
| GSM494685 |
STAT3 bound pre IL21, seq 2 |
| GSM494686 |
STAT3 bound pre IL21 dup, seq 1 |
| GSM494687 |
STAT3 bound pre IL21 dup, seq 2 |
| GSM494688 |
STAT3 bound pre IL21 in WT, ter |
| GSM494689 |
STAT3 bound pre IL21 in WT, 4th experiment |
| GSM494690 |
STAT3 bound post IL21, seq 1 |
| GSM494691 |
STAT3 bound post IL21, seq 2 |
| GSM494692 |
STAT3 bound post IL21 dup, seq 1 |
| GSM494693 |
STAT3 bound post IL21 dup, seq 2 |
| GSM494694 |
STAT3 bound post IL21 in WT, ter |
| GSM494695 |
STAT3 bound post IL21 in WT, quar |
| GSM494696 |
STAT3 bound post IL21 in WT, cinq |
| GSM494697 |
IgG bound post IL6 |
| GSM494698 |
IgG bound post IL2 dup |
| GSM494699 |
IgG bound post IL21 dup |
| GSM494700 |
IgG bound post IL21, ter |
| GSM494701 |
IgG bound post IL21 in WT, quar |
| GSM494702 |
IgG bound post IL21 in B cells |
| GSM494703 |
GIgG bound post IL6 |
| GSM494704 |
GIgG bound post IL21 in B cells |
| GSM494705 |
IRF4 bound pre IL21 in IRF4 KO mice |
| GSM494706 |
IRF4 bound post IL21 in IRF4 KO mice |
| GSM494707 |
STAT3 bound pre IL21 in IRF4 KO mice, first exp |
| GSM494708 |
STAT3 bound pre IL21 in IRF4 KO mice, second exp |
| GSM494709 |
STAT3 bound post IL21 in IRF4 KO mice |
| GSM494710 |
STAT3 bound post IL21 in IRF4 KO mice, second exp |
| GSM494711 |
STAT3 bound post IL21 in IRF4 KO mice, third exp |
|
| Relations |
| SRA |
SRP001688 |
| BioProject |
PRJNA120861 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE19198_RAW.tar |
70.8 Mb |
(http)(custom) |
TAR (of CEL) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...