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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 26, 2012 |
| Title |
Critical Role of STAT5 Transcription Factor Tetramerization for Cytokine Responses and Normal Immune Function (ChIP-Seq and RNA-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Cytokine-activated STAT proteins dimerize and bind to high-affinity motifs, and N-terminal domain-mediated oligomerization of dimers allows tetramer formation and binding to low-affinity tandem motifs, but the functions of dimers versus tetramers are unknown. We generated Stat5a and Stat5b double knock-in (DKI) N-domain mutant mice that form dimers but not tetramers, identified cytokine-regulated genes whose expression required STAT5 tetramers, and defined consensus motifs for dimers versus tetramers. Whereas Stat5- deficient mice exhibited perinatal lethality, DKI mice were viable, indicating that STAT5 dimers were sufficient for survival. Nevertheless, STAT5 DKI mice had fewer CD4+CD25+ T cells, NK cells, and CD8+ T cells, with impaired cytokine-induced proliferation and homeostatic proliferation of CD8+ T cells. DKI CD8+ T cell proliferation following viral infection was diminished and DKI Treg cells did not efficiently control colitis. Thus, tetramerization of STAT5 is dispensable for survival but is critical for cytokine responses and normal immune function.
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| Overall design |
Genome-wide mapping of STAT5A,STAT5B binding in mouse WT and DKI T cells (cultured with or without IL-2 for 1 hr) was conducted. RNA-Seq is conducted in mouse CD8+ T cells (WT and DKI, non-treated or treated with IL-2/IL-15 for 4 hr, 24 hr, 48 hr and 72 hr)
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| Contributor(s) |
Lin J, Li P, Liu D, T Jin H, He J, Rasheed M, Rochman Y, Wang L, Cui K, Liu C, Kelsall BL, Ahmed R, Leonard WJ |
| Citation(s) |
22520852 |
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| Submission date |
Mar 28, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Peng Li |
| E-mail(s) |
peng.li@nih.gov
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| Organization name |
NIH
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| Department |
NHLBI
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| Lab |
LMI
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| Street address |
9000 Rockville Pike
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (2) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
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| Samples (30)
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| This SubSeries is part of SuperSeries: |
| GSE36890 |
Critical Role of STAT5 Transcription Factor Tetramerization for Cytokine Responses and Normal Immune Function |
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| Relations |
| SRA |
SRP011986 |
| BioProject |
PRJNA157369 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE36882_RAW.tar |
571.2 Mb |
(http)(custom) |
TAR (of BED, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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