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 A eukaryotic histone complex can package DNA but is also a cupric reductase that provides biousable Cu1+ for the cell. Eukaryotic histone H3-H4 tetramers contain a putative copper (Cu2+) binding site at the H3-H3′ dimerization interface with unknown function. The coincident emergence of eukaryotes with global oxygenation, which challenged cellular copper utilization, raised the possibility that histones may function in cellular copper homeostasis. We report that the recombinant Xenopus laevis H3-H4 tetramer is an oxidoreductase enzyme that binds Cu2+ and catalyzes its reduction to Cu1+ in vitro. Loss- and gain-of-function mutations of the putative active site residues correspondingly altered copper binding and the enzymatic activity, as well as intracellular Cu1+ abundance and copper-dependent mitochondrial respiration and Sod1 function in the yeast Saccharomyces cerevisiae. The histone H3-H4 tetramer, therefore, has a role other than chromatin compaction or epigenetic regulation and generates biousable Cu1+ ions in eukaryotes.

中文翻译：

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组蛋白 H3-H4 四聚体是一种铜还原酶


组蛋白的酶活性 真核组蛋白作为包装 DNA 的结构元件。然而，它们含有一个铜结合位点，其生物学相关性尚不清楚。铜稳态对于包括线粒体呼吸在内的几个基本真核过程至关重要。阿塔尔等人。假设组蛋白可能在细胞铜利用中发挥关键作用（参见 Rudolph 和 Luger 的观点）。他们采用从体外生物化学到体内遗传和分子分析的多方面方法，发现组蛋白 H3-H4 四聚体是一种氧化还原酶，可催化铜离子还原，从而为各种细胞过程提供生物可用的亚铜离子。这项工作开辟了染色质生物学的新前沿，对真核进化以及人类生物学和疾病具有影响。科学，本期第 14 页。 59；另见 p. 33 真核组蛋白复合物可以包装 DNA，同时也是一种铜还原酶，为细胞提供可生物利用的 Cu1+。真核组蛋白 H3-H4 四聚体在 H3-H3' 二聚化界面处含有一个假定的铜 (Cu2+) 结合位点，其功能未知。真核生物与整体氧合的同时出现，对细胞铜的利用提出了挑战，提出了组蛋白可能在细胞铜稳态中发挥作用的可能性。我们报道重组非洲爪蟾 H3-H4 四聚体是一种氧化还原酶，可结合 Cu2+ 并在体外催化其还原为 Cu1+。假定的活性位点残基的功能丧失和功能获得突变相应地改变了酿酒酵母中的铜结合和酶活性，以及​​细胞内 Cu1+ 丰度和铜依赖性线粒体呼吸和 Sod1 功能。 因此，组蛋白 H3-H4 四聚体具有染色质压缩或表观遗传调控以外的作用，并在真核生物中产生可生物利用的 Cu1+ 离子。