Dr. Steven Henikoff is a Member of the Division of Basic Sciences at Fred Hutchinson Cancer Research Center, and an Investigator with the Howard Hughes Medical Institute.
There has been extraordinary progress in molecular biology during the 50-year span that began with the discovery of the DNA double helix and culminated with the nearly complete specification of our genetic inheritance at level of DNA sequence. The bulk of the eukaryotic genome is packaged into nucleosome particles, each of which comprises an octamer with two copies of each of four core histones–H2A, H2B, H3, and H4–which wrap nearly two turns of DNA. Nucleosomes can be differentiated both by numerous post-translational histone modifications and by incorporation of histone variants, which can replace canonical histones to form nucleosomes with special roles and properties. In contrast to our understanding of genomes, the inheritance of differences in gene expression between cells and tissues and how they are mediated by histones and other chromatin proteins is poorly understood. To better understand inheritance that does not depend on DNA sequence, we apply genomic tools to the study of proteins of the epigenome: histones, transcription factors, nucleosome remodelers, and RNA polymerase II (RNAPII).