Pursuing the Secrets of Histone Proteins: An Amazing Journey with a Remarkable Supporting Cast

Receiving any award for achievements in basic biomedical research, let alone one as prestigious as a Lasker Award, prompts me to ask a simple question: how did I get here?My answer has two parts: not by design and certainly not alone. When I entered the field of histone biology as a postdoc, a rich older literature suggested that histone proteins might be worth a career investment. This was a gamble, but in short, I found histone proteins interesting. While relatively poor in molecular weight, histones were potentially rich in biologically meaningful information, as different gel systems revealed a large variety of patterns in electrophoretic properties. But was any of this heterogeneity physiologically relevant? That histones might be important was supported by their highly conserved nature and their undisputed role as fundamental protein organizers of the chromatin. Well before my time, numerous labs had documented a wealth of post-translational modifications (PTMs) on histones and hypothesized that these PTMs might alter chromatin structure and function by influencing histone-DNA and histone-histone contacts. Eukaryotic genomes demanded packaging within a chromatin environment, but was this packaging anything more than just nature’s clever way to make sure large genomes fit into tight nuclear spaces? I was hoping that there was more gold left to be mined from these ‘‘simple’’ proteins and their welldocumented covalent decorations. I had no plan B, and nothing could have been further from my mind than a Lasker Award.