PMID- 29514917 OWN - NLM STAT- MEDLINE DCOM- 20190617 LR - 20210109 IS - 1540-9538 (Electronic) IS - 0022-1007 (Print) IS - 0022-1007 (Linking) VI - 215 IP - 5 DP - 2018 May 7 TI - Bcl11b, a novel GATA3-interacting protein, suppresses Th1 while limiting Th2 cell differentiation. PG - 1449-1462 LID - 10.1084/jem.20171127 [doi] AB - 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. CI - This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. FAU - Fang, Difeng AU - Fang D AUID- ORCID: 0000-0003-2105-6743 AD - Molecular and Cellular Immunoregulation Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. FAU - Cui, Kairong AU - Cui K AD - Laboratory of Epigenome Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. FAU - Hu, Gangqing AU - Hu G AD - Laboratory of Epigenome Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. FAU - Gurram, Rama Krishna AU - Gurram RK AUID- ORCID: 0000-0002-1956-0249 AD - Molecular and Cellular Immunoregulation Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. FAU - Zhong, Chao AU - Zhong C AD - Molecular and Cellular Immunoregulation Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. FAU - Oler, Andrew J AU - Oler AJ AUID- ORCID: 0000-0002-6310-0434 AD - Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. FAU - Yagi, Ryoji AU - Yagi R AD - Molecular and Cellular Immunoregulation Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. FAU - Zhao, Ming AU - Zhao M AD - Research Technologies Branch, National Institute of Allergy and Infectious Diseases, Rockville, MD. FAU - Sharma, Suveena AU - Sharma S AD - Molecular and Cellular Immunoregulation Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. FAU - Liu, Pentao AU - Liu P AD - School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China. FAU - Sun, Bing AU - Sun B AD - State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China. FAU - Zhao, Keji AU - Zhao K AD - Laboratory of Epigenome Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. FAU - Zhu, Jinfang AU - Zhu J AUID- ORCID: 0000-0002-0117-4745 AD - Molecular and Cellular Immunoregulation Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD jfzhu@niaid.nih.gov. LA - eng GR - ZIA AI001169/ImNIH/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20180307 PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, T-Lymphocyte) RN - 0 (Bcl11b protein, mouse) RN - 0 (CD69 antigen) RN - 0 (Chromatin) RN - 0 (Cytokines) RN - 0 (GATA3 Transcription Factor) RN - 0 (Gata3 protein, mouse) RN - 0 (Lectins, C-Type) RN - 0 (Repressor Proteins) RN - 0 (Tumor Suppressor Proteins) SB - IM MH - Animals MH - Antigens, CD/metabolism MH - Antigens, Differentiation, T-Lymphocyte/metabolism MH - *Cell Differentiation MH - Cell Proliferation MH - Chromatin/metabolism MH - Cytokines/metabolism MH - Epigenesis, Genetic MH - GATA3 Transcription Factor/*metabolism MH - Genome MH - Lectins, C-Type/metabolism MH - Mice, Inbred C57BL MH - Protein Binding MH - Repressor Proteins/*metabolism MH - Th1 Cells/*cytology MH - Th2 Cells/*cytology MH - Tumor Suppressor Proteins/*metabolism PMC - PMC5940260 EDAT- 2018/03/09 06:00 MHDA- 2019/06/18 06:00 PMCR- 2018/11/07 CRDT- 2018/03/09 06:00 PHST- 2017/06/22 00:00 [received] PHST- 2018/01/14 00:00 [revised] PHST- 2018/02/20 00:00 [accepted] PHST- 2018/03/09 06:00 [pubmed] PHST- 2019/06/18 06:00 [medline] PHST- 2018/03/09 06:00 [entrez] PHST- 2018/11/07 00:00 [pmc-release] AID - jem.20171127 [pii] AID - 20171127 [pii] AID - 10.1084/jem.20171127 [doi] PST - ppublish SO - J Exp Med. 2018 May 7;215(5):1449-1462. doi: 10.1084/jem.20171127. Epub 2018 Mar 7.