1100 Fairview Ave N, A1-162, PO Box 19024                                                                                                                     Seattle, WA  98109-1024, USA

 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.

Our recent studies have aimed to understand the elusive relationship between chromatin and epigenetic inheritance. In large part, our focus has been on the universal set of histone variants that replace canonical histones independent of replication. Our studies of the H3.3 replacement variant have led to an appreciation of the role that nucleosome dynamics plays in epigenetic inheritance. We have also introduced powerful strategies for profiling nucleosome dynamics using the classical method of salt fractionation and a novel metabolic labeling strategy, and have introduced a simply affinity-based method for cell-type specific nuclear isolation. Our investigation of the properties of the CenH3 centromere-specific histone variant have led us to describe a novel tetrameric nucleosome, both in its core structure and in its mode of DNA wrapping. In addition, profiling of the universal H2A.Z variant in Arabidopsis has led us to describe a previously unsuspected mutual antagonism between H2A.Z and DNA methylation, and to a new paradigm for gene silencing by DNA methylation that we have extended to a mouse model for cancer. Finally, our high-resolution mapping of DNA methylation differences between Arabidopsis embryos and endosperms has revealed that demethylation of transposable element fragments underlies genomic imprinting.