Beyond Epigenetics: Chromatin as a Metabolic Organelle

Ancestral histones originated before many of the structural and regulatory functions now associated with chromatin, as well as before much of the machinery that writes, removes, and interprets histone modifications. We therefore reasoned that histones might possess an older biochemical activity that provided a selective advantage early in their evolution. We discovered that histone H3 functions as a copper reductase enzyme, converting Cu2+ to bioavailable Cu1+. I will discuss how this enzymatic activity provides a new framework for understanding the evolution and function of the nucleosome, the potential role of histones in eukaryogenesis, and how histone mutations may contribute to human disease.