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| Status |
Public on Mar 05, 2018 |
| Title |
Bcl11b, a Novel GATA3-Interacting Protein, Suppresses Th1 while Limiting Th2 Cell Differentiation (H3K27ac and DNase-Seq) |
| Organism |
Mus musculus |
| Experiment type |
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 histone modification H3K27ac and scDNase-Seq analysis in early and late WT or KO Th2 cells.
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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 |
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| Submission date |
Dec 29, 2017 |
| Last update date |
Feb 11, 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) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (16)
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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 |
| BioProject |
PRJNA427914 |
| SRA |
SRP127732 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE108633_RAW.tar |
6.5 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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