The histone H3-H4 tetramer is a copper reductase enzyme
Narsis Attar, Oscar A. Campos, Maria Vogelauer, Chen Cheng, Yong Xue, Stefan Schmollinger, Łukasz Salwiński, Nathan V. Mallipeddi, Brandon A. Boone, Linda Yen, Sichen Yang, Shannon Zikovich, Jade Dardine, Michael Carey, Sabeeha Merchant, Siavash K. Kurdistani
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