Research Papers:

Up-regulation of IRF-3 expression through GATA-1 acetylation by histone deacetylase inhibitor in lung adenocarcinoma A549 cells

Lu-Lu Wang, Lan-Bo Zhou, Jin Shu, Nan-Nan Li, Hui-Wen Zhang, Rui Jin, Li-Li Zhuang and Guo-Ping Zhou _

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Oncotarget. 2017; 8:75943-75951. https://doi.org/10.18632/oncotarget.18371

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Lu-Lu Wang1, Lan-Bo Zhou2, Jin Shu3, Nan-Nan Li1, Hui-Wen Zhang1, Rui Jin1, Li-Li Zhuang1 and Guo-Ping Zhou1

1Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China

2Grade 2013 Clinical Class 7, The First School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, China

3Department of Pediatric Respiration, Affiliated Wuxi People’s Hospital, Nanjing Medical University, Wuxi, Jiangsu, China

Correspondence to:

Guo-Ping Zhou, email: [email protected]

Keywords: interferon regulatroy factor 3, GATA-1, acetylation, histone deacetylase inhibitor, lung adenocarcinoma

Received: December 20, 2016     Accepted: April 21, 2017     Published: June 06, 2017


Interferon regulatory factor 3 (IRF-3) is an important transcription factor for interferon genes. Although its functional activation by viral infection has been widely explicated, the regulatory mechanism of IRF-3 gene expression in cancer cells is poorly understood. In this study, we demonstrated treatment of lung adenocarcinoma A549 cells with trichostatin A (TSA) and valproic acid (VPA), two different classes of histone deacetylase inhibitors, strongly stimulated IRF-3 gene expression. Truncated and mutated IRF-3 promoter indicated that a specific GATA-1 element was responsible for TSA-induced activation of IRF-3 promoter. Chromatin immunoprecipitation and electrophoretic mobility shift assay showed that TSA treatment increased the binding affinity of GATA-1 to IRF-3 promoter. Using immunoprecipitation assay and immunoblotting, we demonstrated that TSA increased the level of acetylated GATA-1 in A549 cells. In summary, our study implied that TSA enhanced IRF-3 gene expression through increased GATA-1 recruitment to IRF-3 promoter and the acetylation level of GATA-1 in lung adenocarcinoma A549 cells.

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