The McKnight Lab is interested in the targeting and regulation of chromatin modifying proteins and ATP-dependent chromatin remodeling factors in vivo. Because nucleosomes, the fundamental units of chromatin, are intrinsically inhibitory to DNA-dependent processes like transcription, replication, and DNA repair, proper control of their positions and modification state is critical for cellular processes in all eukaryotic organisms. Importantly, aberrant chromatin dynamics is often associated with developmental malfunctions and human cancers. While much has been learned about mechanisms of chromatin modifying and remodeling proteins in vitro, there has been significantly less mechanistic investigation into how their regulation establishes proper nucleosome positions and modification state under changing environmental conditions in vivo (Figure 1). Additionally, relatively little high resolution work has been done to investigate global targeting of chromatin proteins in three dimensions or to determine how dynamic targeting can lead to reproducible changes in chromatin states. Our lab uses interdisciplinary approaches in biochemistry and genomics and is developing new technologies to probe and manipulate chromatin structure using the budding yeast S. cerevisiae as a model system.

  Natural and Synthetic Targeting of Chromatin Proteins