In eukaryotic cells, the DNA genome is tightly packaged in the nucleus by close physical association with small proteins called histones. Chemical modifications of the histone proteins can loosen or strengthen their association with DNA. Such chemical changes have been correlated indirectly with changes in how the information in DNA is used, but to date, direct cause-and-effect tests of the outcome of histone modifications on DNA function have not been feasible. This project will develop and apply new cutting-edge tools to enable direct measurements of how histone modifications impact the function of DNA. The results will provide deeper understanding of normal regulatory mechanisms and provide a framework for understanding how they contribute to proper growth and development. In addition to the research goals, the project will also establish educational outreach activities to attract younger generations to science through summer research opportunities and seminar series for local high school students as well as undergraduate students.
Regulation of gene expression is tightly linked to mechanisms that package DNA inside the nucleus. DNA is wrapped around histone proteins to form chromatin fiber. Small chemical modifications on histone proteins or DNA, which are called epigenetic modifications, are associated with gene activation or repression. Understanding the molecular details of how epigenetic modifications regulate gene expression has immediate implications for better understanding of crucial developmental processes in both animals and plants. However, due to technical limitations, the causal relationship between the presence of an epigenetic mark and gene function in the chromatin is not proven. This project will utilize cutting edge CRISPR-Cas9-based genome editing tools to deposit specific epigenetic marks at target genomic sites to study their functional roles over time. By precisely manipulating temporal and spatial locus-specific epigenetic marks, the project will address fundamental cause-and-effect mechanisms relating epigenetic information to changes in gene expression.
