Bcl11b, a novel GATA3-interacting protein, suppresses Th1 while limiting Th2 cell differentiation
| Autor: | Jinfang Zhu, Kairong Cui, Bing Sun, Andrew J. Oler, Ryoji Yagi, Difeng Fang, Pentao Liu, Suveena Sharma, Rama Krishna Gurram, Gangqing Hu, Ming Zhao, Keji Zhao, Chao Zhong |
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| Rok vydání: | 2018 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte 0301 basic medicine BCL11B Cellular differentiation Immunology GATA3 Transcription Factor Article Epigenesis Genetic 03 medical and health sciences Th2 Cells 0302 clinical medicine Antigens CD Gene expression Animals Immunology and Allergy Lectins C-Type Epigenetics Gene Transcription factor Research Articles Cell Proliferation Regulation of gene expression Genome Chemistry Tumor Suppressor Proteins GATA3 Cell Differentiation Th1 Cells Chromatin 3. Good health Cell biology Mice Inbred C57BL Repressor Proteins 030104 developmental biology 030220 oncology & carcinogenesis Cytokines Protein Binding |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | Bcl11b, a novel component of GATA3-containing transcriptional complex, inhibits Th2 cytokine production both in vitro and in vivo. Genome-wide analysis indicates that the Bcl11b/GATA3 complex not only limits the magnitude of Th2 response but also suppresses Th1-specific gene expression. 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 show 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 colocalize 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 genes (from RNA sequencing), cobinding patterns (from chromatin immunoprecipitation sequencing), and Bcl11b-modulated epigenetic modification and gene accessibility 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. |
| Databáze: | OpenAIRE |
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