To maintain the differentiated tissues in any organism, cell-type specific genes must remain "on" for the lifetime of the organism in one cell type, and "off" for the lifetime of the organism in other cells. Thus, the same gene can be kept in an "on" state across numerous cell divisions in one cell, but be kept in an "off" state across numerous cell divisions in a nearby cell. This type of regulation, frequently referred to as epigenetic regulation, occurs at least in part by maintaining different states of the chromatin over a gene when it is on as compared to when it is off. When a gene is maintained in an off state, the chromatin packaging that gene is maintained in a state that inhibits transcription factor function, and thus blocks transcription of the gene. When a gene is maintained in an on state, the chromatin is maintained in a configuration that is permissive for transcription.

The nucleosome is the fundamental building block of chromatin, and genetic studies imply that altering nucleosome structure and plays a central role in epigenetic regulation. Research projects in the Kingston laboratory are designed to characterize, using biochemical approaches, protein complexes that are involved in epigenetic regulation. One set of projects focuses on the mechanism of ATP-dependent remodeling complexes, with the goal of understanding how these complexes use the energy of ATP hydrolysis to alter nucleosome structure and how these alterations can contribute to overall chromosome dynamics and to transcriptional regulation. A second set of projects focuses on the Polycomb-group (PcG) of genes. Complexes of that are encoded by PcG genes are required to maintain chromatin in a repressed state, and current projects use purified forms of these complexes to characterize how the complexes regulate chromatin structure and transcription of chromatinized templates. A key area of future analysis will be to understand how these and other complexes contribute to the regulation of higher order chromatin structure.