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Nickel compounds are novel inhibitors of histone H4 acetylation

Broday, Limor and Peng, Wu and Kuo, Min-Hao and Salnikow, Konstantin and Zoroddu, Maria Antonietta and Costa, Max (2000) Nickel compounds are novel inhibitors of histone H4 acetylation. Cancer Research, Vol. 60 (2), p. 238-241. eISSN 0008-5472. Article.

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Environmental factors influence carcinogenesis by interfering with a variety of cellular targets. Carcinogenic nickel compounds, although generally inactive in most gene mutation assays, induce chromosomal damage in heterochromatic regions and cause silencing of reporter genes when they are located near telomere or heterochromatin in either yeast or mammalian cells. We studied the effects of nickel on the lysine acetylation status of the NH2-terminal region of histone H4. At nontoxic levels, nickel decreased the levels of histone H4 acetylation in vivo in both yeast and mammalian cells, affecting only lysine 12 in mammalian cells and all of the four lysine residues in yeast. In yeast, lysine 12 and 16 were more greatly affected than lysine 5 and 8. Interestingly, a histidine Ni2+ anchoring site is found at position 18 from the NH2-terminal tail of H4. Nickel was also found to inhibit the acetylation of H4 in vitro using purified recombinant histone acetyltransferase. To our knowledge, this is the first agent shown to decrease histone H4 acetylation at nontoxic levels.

Item Type:Article
ID Code:5307
Uncontrolled Keywords:Nickel compounds, carcinogenesis, histone H4
Subjects:Area 03 - Scienze chimiche > CHIM/03 Chimica generale e inorganica
Divisions:001 Università di Sassari > 01 Dipartimenti > Chimica
Publisher:American Association for Cancer Research
Deposited On:12 Jan 2011 10:19

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