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Chromatin state dynamics during NK cell activation
- Source :
- Oncotarget
- Publication Year :
- 2017
- Publisher :
- Impact Journals LLC, 2017.
-
Abstract
- // Yang Li 1,* , Jin Wang 1,* , Jie Yin 1 , Xinhua Liu 2 , Minghang Yu 1 , Ting Li 1 , Han Yan 1 and Xi Wang 1 1 Department of Cell Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Laboratory of Epigenetics in Development and Tumorigenesis, Tianjin Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, China 2 Department of Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China * Yang Li and Jin Wang have contributed equally to this work Correspondence to: Xi Wang, email: // Keywords : NK cell, activation, histone modification, poised state, small molecule inhibitor, Immunology and Microbiology Section, Immune response, Immunity Received : December 08, 2016 Accepted : March 16, 2017 Published : March 29, 2017 Abstract Studies of Natural Killer (NK) cell cytotoxicity have mainly focused on the balance of activating and inhibitory receptors, signaling transduction, calcium influx, formation of immune synapse, and cytolytic degranulation. However, little is known about the chromatin state of NK cells and the impact of its changes during target recognition. In this study, we investigate the contribution of chromatin state dynamics during NK cell activation by comprehensively analyzing a set of microarray data and two sets of Chromatin Immunoprecipitation-Sequencing (ChIP-seq) data. We find that the expression of several histone demethylases and methyltransferases was influenced upon stimulation. Furthermore, we notice that a series of genes, including PI3KCA, NFATC1and TNFSF9, which play important roles during NK cell activation, were at ‘poised’ state prior to activation, and that modifications of H3K4me3 and H3K27me3 on these promotors were sensitive to stimulation with Phorbol Myristate Acetate (PMA) and Ionomycin (Iono) in the NK92MI cell line. Finally, we demonstrate that a series of small molecule inhibitors, which are specific to H3K4 and H3K27 modification, enhance degranulation or the expression levels of IFN-γ and TNF-α. Our results suggest that the histone modification state has a profound impact on NK cell activation, and provide novel insights into the regulation of NK cellular cytotoxicity and immunoregulatory function by chromatin state dynamics.
- Subjects :
- 0301 basic medicine
Cytotoxicity, Immunologic
Methyltransferase
medicine.disease_cause
Lymphocyte Activation
Cell Degranulation
Immunological synapse
Histones
03 medical and health sciences
0302 clinical medicine
medicine
Humans
NK cell
histone modification
Gene Regulatory Networks
Epigenetics
Immune response
Histone Demethylases
biology
Microarray analysis techniques
Gene Expression Profiling
Research Paper: Immunology
Immunity
small molecule inhibitor
Histone-Lysine N-Methyltransferase
Chromatin Assembly and Disassembly
Chromatin
Cell biology
Killer Cells, Natural
030104 developmental biology
Histone
Oncology
Gene Expression Regulation
030220 oncology & carcinogenesis
Immunology
biology.protein
Histone Methyltransferases
H3K4me3
Immunology and Microbiology Section
Cytokines
activation
Carcinogenesis
poised state
Subjects
Details
- Language :
- English
- ISSN :
- 19492553
- Volume :
- 8
- Issue :
- 26
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....ef5c4346791448a0fb7a9426b8d67aa9