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| Status |
Public on Jan 18, 2019 |
| Title |
RNA-seq and ChIP-seq to study how transcription factor Foxp1 regulates Foxp3 binding to chromatin and coordinates regulatory T cell function |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Regulatory T (Treg) cells, whose differentiation and function are controlled by transcription factor Foxp3, express high amounts of a closely related family member Foxp1, which is also expressed in quiescent naive T cells. Here we explored Foxp1 function in Treg cells. We found that a large number of Foxp3-bound genomic sites in Treg cells were occupied by Foxp1 in both Treg and conventional T cells. In Treg cells, Foxp1 markedly increased Foxp3 binding to these sites, which were enriched for canonic forkhead and Ets binding motifs. Foxp1 deficiency in Treg cells resulted in their impaired function and competitive fitness associated with markedly reduced CD25 expression and interleukin-2 (IL-2) responsiveness, diminished CTLA-4 and increased SATB1 expression. The characteristic patterns of CD25, Foxp3, and CTLA-4 expression in Treg cells were rescued, at least in part, upon strong IL-2 signaling. Our studies suggest that in addition to the Foxp1-mediated regulation of quiescence that is common to Treg and conventional T cells, Foxp1 has an essential non-redundant function in Treg cells by enforcing Foxp3-mediated regulation of gene expression and enabling efficient IL-2 signaling in these cells.
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| Overall design |
Foxp1 ChIP-seq in Treg (triplicates) and conventional T cells (duplicates), with genetic controls; Foxp3 ChIP-seq in wildtype (duplicates) and Foxp1-deficient (triplicates) Treg cells, with genetic controls; RNA-seq in naïve and activated wildtype and Foxp1-deficient Treg cell (triplicates)
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| Contributor(s) |
Konopacki C, Pritykin Y, Rubtsov Y, Leslie C, Rudensky A |
| Citation(s) |
30643266 |
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| Submission date |
Oct 15, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Yuri Pritykin |
| Organization name |
Princeton University
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| Street address |
245 Carl Icahn Lab, Lewis-Sigler Institute for Integrative Genomics
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| City |
Princeton |
| State/province |
NJ |
| ZIP/Postal code |
08540 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (29)
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| GSM3430732 |
Foxp1 ChIP-seq in Foxp1- Treg (genetic control) |
| GSM3430733 |
Foxp1 ChIP-seq in conventional T cells, rep1 |
| GSM3430734 |
Foxp1 ChIP-seq in conventional T cells, rep2 |
| GSM3430735 |
Foxp3 ChIP-seq in Foxp1+ Treg, rep1 |
| GSM3430736 |
Foxp3 ChIP-seq in Foxp1+ Treg, rep2 |
| GSM3430737 |
Foxp3 ChIP-seq in Foxp1- Treg, rep1 |
| GSM3430738 |
Foxp3 ChIP-seq in Foxp1- Treg, rep2 |
| GSM3430739 |
Foxp3 ChIP-seq in Foxp1- Treg, rep3 |
| GSM3430740 |
Foxp3 ChIP-seq in Foxp1+ conventional T cells, rep1 (genetic control) |
| GSM3430741 |
Foxp3 ChIP-seq in Foxp1+ conventional T cells, rep2 (genetic control) |
| GSM3430742 |
Foxp3 ChIP-seq in Foxp1+ conventional T cells, rep3 (genetic control) |
| GSM3430743 |
Foxp3 ChIP-seq in Foxp1- conventional T cells, rep1 (genetic control) |
| GSM3430744 |
Foxp3 ChIP-seq in Foxp1- conventional T cells, rep2 (genetic control) |
| GSM3430745 |
Foxp3 ChIP-seq in Foxp1- conventional T cells, rep3 (genetic control) |
| GSM3430746 |
RNA-seq in naïve Foxp1+ Treg cells, rep1 |
| GSM3430747 |
RNA-seq in naïve Foxp1+ Treg cells, rep2 |
| GSM3430748 |
RNA-seq in naïve Foxp1+ Treg cells, rep3 |
| GSM3430749 |
RNA-seq in naïve Foxp1- Treg cells, rep1 |
| GSM3430750 |
RNA-seq in naïve Foxp1- Treg cells, rep2 |
| GSM3430751 |
RNA-seq in naïve Foxp1- Treg cells, rep3 |
| GSM3430752 |
RNA-seq in activated Foxp1+ Treg cells, rep1 |
| GSM3430753 |
RNA-seq in activated Foxp1+ Treg cells, rep2 |
| GSM3430754 |
RNA-seq in activated Foxp1+ Treg cells, rep3 |
| GSM3430755 |
RNA-seq in activated Foxp1- Treg cells, rep1 |
| GSM3430756 |
RNA-seq in activated Foxp1- Treg cells, rep2 |
| GSM3430757 |
RNA-seq in activated Foxp1- Treg cells, rep3 |
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| Relations |
| BioProject |
PRJNA496510 |
| SRA |
SRP165789 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE121279_peaks-foxp1.txt.gz |
385.2 Kb |
(ftp)(http) |
TXT |
| GSE121279_peaks-foxp3.txt.gz |
937.9 Kb |
(ftp)(http) |
TXT |
| GSE121279_rnaseq-counts-raw.txt.gz |
551.5 Kb |
(ftp)(http) |
TXT |
| GSE121279_rnaseq-foxp1fl-over-wt-results.txt.gz |
424.3 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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