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| Status |
Public on Nov 24, 2012 |
| Title |
STATs Shape the Active Enhancer Landscape of T Cell Populations |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Signaling pathways are intimately involved in cellular differentiation, allowing cells to respond to their environment by regulating gene expression. While enhancers are recognized as key elements that regulate selective gene expression, the interplay between signaling pathways and actively used enhancer elements is not clear. Here, we use CD4+ T cells as a model of differentiation, mapping the acquisition of cell-type-specific enhancer elements in T-helper 1 (Th1) and Th2 cells. Our data establish that STAT proteins have a major impact on the acquisition of lineage-specific enhancers and the suppression of enhancers associated with alternative cell fates. Transcriptome analysis further supports a functional role for enhancers regulated by STATs. Importantly, expression of lineage-defining master regulators in STAT-deficient cells fails to fully recover the chromatin signature of STAT-dependent enhancers. Thus, these findings point to a critical role of STATs as environmental sensors in dynamically molding the specialized enhancer architecture of differentiating cells.
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| Overall design |
Active enhancer elements were defined as p300-high/H3K4me1-high. Using ChIP-seq, we mapped active enhancer landscapes of two CD4+ T helper cells, Th1 and Th2. To investigate the effect of STAT proteins on this landscape, we profiled active enhancers in the absence of STATs. Overall, STATs deficiency had a major impact on recruitment of p300. In addition, ectopic expression of master regulators T-bet and GATA3 in STAT-deficient cells failed to recover most active enhancers.
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| Contributor(s) |
Vahedi G, Takahashi H, Nakayamada S, Sun H, Sartorelli V, Kanno Y, O’Shea JJ |
| Citation(s) |
23178119, 23555662 |
| Submission date |
Aug 29, 2012 |
| Last update date |
Feb 12, 2020 |
| Contact name |
Golnaz Vahedi |
| Organization name |
National Institutes of Health
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| Department |
NIAMS
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| Lab |
Lymphocyte Cell Biology Section
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| Street address |
9000 Rockville Pike Bldg 10 Rm 13C101A
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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 (42)
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| Relations |
| BioProject |
PRJNA174565 |
| SRA |
SRP015458 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE40463_RAW.tar |
1.9 Gb |
(http)(custom) |
TAR (of BEDGRAPH, BIGWIG, RPKM) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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