Chromatin complexes (consisting of histone and nonhistone proteins, RNA molecules and DNA within the nucleus) keep a reign on transcription factor binding to maintain appropriate transcription patterns in eukaryotes. Our laboratory has been studying the conserved protein structures that specifically mark and recognize histone and nucleic acid components in chromatin of yeast, flies, plants and mammals. We have characterized lysine methyltransferases and methyllysine recognition factors to understand the putative function of histone lysine methylation in maintenance and memory of active and repressed transcription phenomena. Complementary biophysical and chemical approaches have revealed structural and thermodynamic principles of chromatin regulations, uncovering an unexpected diversity of signaling and regulation among eukaryotes. Chromatin/epigenetic regulations in humans involve complex modulations of transcription factor binding and signaling responses not readily amenable to therapeutic intervention. We plan to delineate specific mechanisms of transcription control in cardiovascular disease and diabetes. We are also interested in identifying drug or tool compounds that target the active sites in chromatin/transcription factors.

Parallel efforts are devoted to delineating the basis for maintenance and memory of active and repressed transcription phenomena in eukaryotic pathogens that infect humans. By understanding the basis for chromatin regulation in pathogens we hope to identify diagnostic tools and therapeutic targets. This list of protozoan organisms often affect the human intestine and cause a variety of diseases. We chose to focus on Entamoeba histolytica, the cause of amoebiasis, because its genome is annotated (encodes about 8000 genes), gene transcription levels have been measured in both the dormant cyst and the active trophozoite stages, and most importantly, there is an established mouse model for investigating the disease. We noticed a major deviation in the histone language of this organism and have focused our investigations on the activity of lysine methyltransferases and methyllysine recognition factors.