Nickel ions increase histone H3 lysine 9 dimethylation and induce transgene silencing.

Molecular and Cellular Biology
Haobin ChenMax Costa

Abstract

We have previously reported that carcinogenic nickel compounds decreased global histone H4 acetylation and silenced the gpt transgene in G12 Chinese hamster cells. However, the nature of this silencing is still not clear. Here, we report that nickel ion exposure increases global H3K9 mono- and dimethylation, both of which are critical marks for DNA methylation and long-term gene silencing. In contrast to the up-regulation of global H3K9 dimethylation, nickel ions decreased the expression and activity of histone H3K9 specific methyltransferase G9a. Further investigation demonstrated that nickel ions interfered with the removal of histone methylation in vivo and directly decreased the activity of a Fe(II)-2-oxoglutarate-dependent histone H3K9 demethylase in nuclear extract in vitro. These results are the first to show a histone H3K9 demethylase activity dependent on both iron and 2-oxoglutarate. Exposure to nickel ions also increased H3K9 dimethylation at the gpt locus in G12 cells and repressed the expression of the gpt transgene. An extended nickel ion exposure led to increased frequency of the gpt transgene silencing, which was readily reversed by treatment with DNA-demethylating agent 5-aza-2'-deoxycytidine. Collectively, our...Continue Reading

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Citations

Jul 20, 2007·Reviews in Endocrine & Metabolic Disorders·Wan-yee Tang, Shuk-mei Ho
Jan 1, 2009·Metallomics : Integrated Biometal Science·Adriana Arita, Max Costa
Apr 5, 2012·Metallomics : Integrated Biometal Science·Yana ChervonaMax Costa
Oct 6, 2010·Antioxidants & Redox Signaling·Anthony R Cyr, Frederick E Domann
Mar 7, 2008·Carcinogenesis·Xue ZhouMax Costa
Apr 21, 2009·Carcinogenesis·Qin LiMax Costa
Oct 21, 2010·Nucleic Acids Research·Luke GaughanCraig N Robson
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Dec 1, 2012·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Adriana AritaMax Costa
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Mar 24, 2010·The Mount Sinai Journal of Medicine, New York·Yevgeniya PozharnyMen-Jean Lee

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