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Hyperacetylation of Histone H3K9 Involved in the Promotion of Abnormally High Transcription of the gdnf Gene in Glioma Cells

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Abstract

The mechanism underlying abnormally high transcription of the glial cell line-derived neurotrophic factor (GDNF) gene in glioma cells is not clear. In this study, to assess histone H3K9 acetylation levels in promoters I and II of the gdnf gene in normal human brain tissue, low- and high-grade glioma tissues, normal rat astrocytes, and rat C6 glioblastoma cells, we employed chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR), real-time PCR, and a pGL3 dual fluorescence reporter system. We also investigated the influence of treatment with curcumin, a histone acetyltransferase inhibitor, and trichostatin A (TSA), a deacetylase inhibitor, on promoter acetylation and activity and messenger RNA (mRNA) expression level of the gdnf gene in C6 cells. Compared to normal brain tissue, H3K9 acetylation in promoters I and II of the gdnf gene increased significantly in high-grade glioma tissues but not in low-grade glioma tissues. Moreover, H3K9 promoter acetylation level of the gdnf gene in C6 cells was also remarkably higher than in normal astrocytes. In C6 cells, curcumin markedly decreased promoter II acetylation and activity and GDNF mRNA expression. Conversely, all three measurements were significantly increased following TSA treatment. Our results suggest that histone H3K9 hyperacetylation in promoter II of the gdnf gene might be one of the reasons for its abnormal high transcription in glioma cells.

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Acknowledgments

This project was supported by the National Natural Science Foundation of China (Grant numbers 31271358 and 81101899), Natural Science Foundation of Jiangsu Province (08KJB180011 and BK20130212), China Postdoctoral Science Foundation funded project (2013M540466), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

    Zheng-Quan Yu, Hai-Bo Ni, Ze-Hao Liu, Jian-Cun Wang & Qing-Xian Ren

  2. Department of Neurobiology and Anatomy, Xuzhou Medical College, Xuzhou, Jiangsu, China

    Bao-Le Zhang, Jian-Bing Mo, Ye Xiong, Rui-Qin Yao & Dian-Shuai Gao

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  1. Zheng-Quan Yu
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  2. Bao-Le Zhang
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Correspondence to Dian-Shuai Gao.

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Zheng-Quan Yu and Bao-Le Zhang contributed equally to this work.

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Yu, ZQ., Zhang, BL., Ni, HB. et al. Hyperacetylation of Histone H3K9 Involved in the Promotion of Abnormally High Transcription of the gdnf Gene in Glioma Cells. Mol Neurobiol 50, 914–922 (2014). https://doi.org/10.1007/s12035-014-8666-0

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  • DOI: https://doi.org/10.1007/s12035-014-8666-0

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