期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 215, 期 5, 页码 1449-1462出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20171127
关键词
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资金
- National Institute of Allergy and Infectious Diseases [1-ZIA-AI001169]
- National Heart, Lung, and Blood Institute (National Institutes of Health)
- National Natural Science Foundation of China [81761128009]
- Grants-in-Aid for Scientific Research [15K08523] Funding Source: KAKEN
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI001169] Funding Source: NIH RePORTER
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.
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