Project 461707

While all cells within an individual organism contain nearly identical DNA, each cell type and tissue has distinct properties. Those properties are determined by a number of "epigenetic" modifications, such as histone and DNA methylation, which dictate which genes and at what levels may be expressed in a given cell. Proper patterns of epigenetic modifications and essential for normal development and maintenance of cell identity. Epigenetic defects result in disease and cancer. We and others have shown that there exists a number of interdependencies between distinct histone and DNA modifications, which are mediated by the ability of various enzymes to recognize and "read" the histone code, and subsequently "write" downstream components of the code on the chromatin. Here, we propose to use cell culture systems, CRISPR genome editing techniques, and time series experiments to study the order of events occurring during the establishment of epigenetic patterns and further elucidate the relationship between different chromatin modifications. We aim to identify epigenetic interactions that are detrimental to cancer cells and investigate their downstream effects.