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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 05, 2018 |
| Title |
Bcl11b- and GATA3-mediated gene regulation in Th2 cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
GATA-binding protein 3 (GATA3) acts as the master transcription factor for type 2 T helper (Th2) cell differentiation and function. However, it is still elusive how GATA3 function is precisely regulated in Th2 cells. Here, we report that the transcription factor B cell lymphoma 11b (Bcl11b), a previously unknown component of GATA3 transcriptional complex, is involved in GATA3-mediated gene regulation. Bcl11b binds to GATA3 through protein-protein interaction, and they co-localize at many important cis-regulatory elements in Th2 cells. The expression of type 2 cytokines, including IL-4, IL-5 and IL-13, is up-regulated in Bcl11b-deficient Th2 cells both in vitro and in vivo; such up-regulation is completely GATA3-dependent. Genome-wide analyses of Bcl11b- and GATA3-regulated gene (from RNA-Seq), co-binding pattern (from ChIP-Seq), and Bcl11b-mediated epigenetic changes (in H3K27ac and DHSs) suggest that GATA3/Bcl11b complex is involved in limiting Th2 gene expression, as well as in inhibiting non-Th2 gene expression. Thus, Bcl11b controls both GATA3-mediated gene activation and repression in Th2 cells.
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| Overall design |
Naïve CD4 T cells were isolated from Bcl11bfl/fl-CreERT2 mice and cultured under Th2 conditions with or without 4-OHT for 4 days (early Th2 cells). Naïve CD4 T cells were isolated from Bcl11bfl/fl-CreERT2 mice and cultured under Th2 conditions for 4 days. Then, after resting in IL-2-containing medium for one day, the primed cells were further cultured under Th2 conditions with or without 4-OHT for 4 days (late Th2 cells). ChIP-Seq of Bcl11b and GATA3 analysis in early and late WT or KO Th2 cells. RNA-seq for early and late WT or KO Th2 cells, with 2 replicates. Raw data is in SRP104190.
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| Contributor(s) |
Fang D, Cui K, Hu G, Gurram RK, Zhong C, Oler AJ, Yagi R, Zhao M, Sharma S, Liu P, Sun B, Zhao K, Zhu J |
| Citation(s) |
29514917 |
| BioProject |
PRJNA383417 |
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| Submission date |
Jan 11, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Andrew J Oler |
| E-mail(s) |
[email protected]
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| Organization name |
NIAID/NIH
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| Department |
Bioinformatics and Computational Biosciences Branch (BCBB)
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| Lab |
Computational Biology Section
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| Street address |
31 Center Drive, Room 3B62E
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (19)
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| GSM2931793 |
RNA-seq of Mus musculus: Th2 Early Bcl11b WT Rep 1 |
| GSM2931794 |
RNA-seq of Mus musculus: Th2 Early Bcl11b WT Rep 2 |
| GSM2931795 |
RNA-seq of Mus musculus: Th2 Early Bcl11b KO Rep 1 |
| GSM2931796 |
RNA-seq of Mus musculus: Th2 Early Bcl11b KO Rep 2 |
| GSM2931797 |
RNA-seq of Mus musculus: Th2 Late Bcl11b WT Rep 1 |
| GSM2931798 |
RNA-seq of Mus musculus: Th2 Late Bcl11b WT Rep 2 |
| GSM2931799 |
RNA-seq of Mus musculus: Th2 Late Bcl11b KO Rep 1 |
| GSM2931800 |
RNA-seq of Mus musculus: Th2 Late Bcl11b KO Rep 2 |
| GSM2931801 |
RNA-seq of Mus musculus: Th2 Early Gata3 WT Rep 1 |
| GSM2931802 |
RNA-seq of Mus musculus: Th2 Early Gata3 WT Rep 2 |
| GSM2931803 |
RNA-seq of Mus musculus: Th2 Early Gata3 KO Rep 1 |
| GSM2931804 |
RNA-seq of Mus musculus: Th2 Early Gata3 KO Rep 2 |
| GSM2931805 |
RNA-seq of Mus musculus: Th2 Late Gata3 WT Rep 1 |
| GSM2931806 |
RNA-seq of Mus musculus: Th2 Late Gata3 WT Rep 2 |
| GSM2931807 |
RNA-seq of Mus musculus: Th2 Late Gata3 KO Rep 1 |
| GSM2931808 |
RNA-seq of Mus musculus: Th2 Late Gata3 KO Rep 2 |
| GSM2931809 |
ChIP-seq of Mus musculus: Th2 WT Bcl11b |
| GSM2931810 |
ChIP-seq of Mus musculus: Th2 WT Gata3 |
| GSM2931811 |
ChIP-seq of Mus musculus: Th2 WT Input |
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| This SubSeries is part of SuperSeries: |
| GSE109109 |
Bcl11b, a Novel GATA3-Interacting Protein, Suppresses Th1 while Limiting Th2 Cell Differentiation |
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| Relations |
| SRA |
SRP104190 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE109107_RAW.tar |
10.7 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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