|
| Status |
Public on Sep 20, 2012 |
| Title |
A validated regulatory network for Th17 cell specification |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Th17 cells have critical roles in mucosal defense and are major contributors to inflammatory disease. Their differentiation requires the nuclear hormone receptor RORγt working with multiple other essential transcription factors (TFs). We have used an iterative systems approach, combining genome-wide TF occupancy, expression profiling of TF mutants, and expression time series to delineate the Th17 global transcriptional regulatory network. We find that cooperatively-bound BATF and IRF4 contribute to initial chromatin accessibility, and with STAT3 initiate a transcriptional program that is then globally tuned by the lineage-specifying TF RORγt, which plays a focal deterministic role at key loci. Integration of multiple datasets allowed inference of an accurate predictive model that we computationally and experimentally validated, identifying multiple new Th17 regulators, including Fosl2, a key determinant of cellular plasticity. This interconnected network can be used to investigate new therapeutic approaches to manipulate Th17 functions in the setting of inflammatory disease.
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| |
|
| Overall design |
143 RNA-seq, 83 ChIP-seq, 65 ChIP-seq controls, and 16 FAIRE-seq
|
| |
|
| Contributor(s) |
Ciofani M, Madar A, Galan C, Sellars M, Mace K, Pauli F, Agarwal A, Huang W, Parkurst CN, Muratet M, Newberry KM, Meadows S, Greenfield A, Yang Y, Jain P, Kirigin FK, Birchmerier C, Wagner EF, Murphy KM, Myers RM, Bonneau R, Littman DR |
| Citation(s) |
23021777 |
| |
| Submission date |
Sep 17, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Ashish Agarwal |
| Organization name |
Solvuu
|
| Street address |
150 E 44th St #27E
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10017 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (307)
|
|
| Relations |
| BioProject |
PRJNA175364 |
| SRA |
SRP015773 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE40918_Inferelator_Immgen.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE40918_Inferelator_RNAseq.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
| GSE40918_RAW.tar |
132.9 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE40918_README_supplementary_files.txt |
4.0 Kb |
(ftp)(http) |
TXT |
| GSE40918_Th17.batf.wt.vs.Th17.batf.ko_Aug_2_2012.txt.gz |
848.2 Kb |
(ftp)(http) |
TXT |
| GSE40918_Th17.fosl2.wt.vs.Th17.fosl2.ko_Aug_2_2012.txt.gz |
841.5 Kb |
(ftp)(http) |
TXT |
| GSE40918_Th17.hif1a.wt.vs.Th17.hif1a.ko_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.ikzf3.wt.vs.Th17.ikzf3.ko_Aug_2_2012.txt.gz |
784.8 Kb |
(ftp)(http) |
TXT |
| GSE40918_Th17.irf4.wt.vs.Th17.irf4.ko_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.maf.wt.vs.Th17.maf.ko_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.rorc.wt.vs.Th17.rorc.ko_Aug_2_2012.txt.gz |
822.1 Kb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hRPMI.vs.Th17.siEtv6.24hRPMI_Aug_2_2012.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siAes.24hScreen_Aug_2_2012.txt.gz |
816.7 Kb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siAtf6.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siBcl11b.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siCcr6.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siCrem.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siDdit3.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siEgr2.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siId2.24hScreen_Aug_2_2012.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siInhba.24hScreen_Aug_2_2012.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siJmjd6.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siKdm6b.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siLef1.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siNfatc2.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siPrkrir.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siRorc.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siSatb1.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siSirt2.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siSki.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siTrib3.24hScreen_Aug_2_2012.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.siNonTar.24hScreen.vs.Th17.siZfp36l2.24hScreen_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_Th17.stat3.wt.vs.Th17.stat3.ko_Aug_2_2012.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE40918_pCRMs_5TFs_th17.txt.gz |
3.7 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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