Nickel interaction with metal binding sequences of histone H4

Nickel compounds are well known as human carcinogens.[1] The leading concepts in nickel
carcinogenesis involves oxidative promutagenic DNA damage and epigenetic effects in
chromatin resulting from nickel binding inside the cell nucleus. The nuclear proteins, and in
particular the most abundant among them, the histones, are able to compete for metal ions with
even higher affinity metal binding sites in other less abundant nuclear proteins or smaller
molecules. Phagocytosis of insoluble particles of Ni3S2 by either macrophages or epithelial cells
causes buildup of very high levels of nickel inside the cells after its intracellular dissolution
catalyzed by the acidic pH of endocytic vacuoles, thus providing a continuous source of Ni(II)
ions.
We investigated the issue of Ni(II) binding within the histone octamer. Using histone
sequences in conjuction with the structural data we identified a binding site for Ni(II) ions located
in the N-terminal tail of the histone H4.