Nickel binding to the N-tail of histone H4: an NMR study

Nickel has been shown to be an essential trace element involved in the metabolism of several species of bacteria, archea, plant and may yet be found to play a role in the metabolism of higher organisms. However, the carcinogenicity of certain nickel compounds has been confirmed by the combination of epidemiological evidence in humans and carcinogenesis bioassays in animals. The molecular mechanisms of nickel-induced carcinogenesis include interactions of this metal with major chromatin components causing alterations in gene expression rather than by direct DNA damage. We have previously reported that nickel is a potent suppressor of histone H4 acetylation, in both yeast and mammalian cells. It has preference to specific lysine residues in the N-terminal tail of histone H4, in which the sites of acetylating are clustered. Here we present our recent results on the coordination ability of Ni(II) to the N-terminal tail of histone H4 using NMR spectroscopy. A series of 1D, 2D Tcosy and Noesy H NMR spectra of the tail with increasing nickel concentration to the final molar ratio 1:1, were acquired, and the data we collected allowed us to calculate a structural model for the square planar complex formed by the Ni(II) ion and our peptide, confirming that the N-terminal tail of histone H4 is a suitable binding site for Nickel ions