The histone H3-H4 tetramer is a copper reductase enzyme

Abstract

Enzymatic activity of histones Eukaryotic histones serve as structural elements to package DNA. However, they contain a copper-binding site for which the biological relevance is unknown. Copper homeostasis is critical for several fundamental eukaryotic processes, including mitochondrial respiration. Attar et al. hypothesized that histones may play a critical role in cellular copper utilization (see the Perspective by Rudolph and Luger). Using a multifaceted approach ranging from in vitro biochemistry to in vivo genetic and molecular analyses, they found that the histone H3-H4 tetramer is an oxidoreductase enzyme that catalyzes reduction of cupric ions, thereby providing biologically usable cuprous ions for various cellular processes. This work opens a new front for chromatin biology, with implications for eukaryotic evolution and human biology and disease. Science , this issue p. 59 ; see also p. 33