Oncotarget

Research Papers: Immunology:

Chromatin state dynamics during NK cell activation

Yang Li, Jin Wang, Jie Yin, Xinhua Liu, Minghang Yu, Ting Li, Han Yan and Xi Wang _

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Oncotarget. 2017; 8:41854-41865. https://doi.org/10.18632/oncotarget.16688

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Abstract

Yang Li1,*, Jin Wang1,*, Jie Yin1, Xinhua Liu2, Minghang Yu1, Ting Li1, Han Yan1 and Xi Wang1

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.


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