In complex genomes like those in plants and mammals, the DNA is selectively modified by chemical addition of methyl groups. The goal of this research is to understand how enzymes that methylate DNA locate the correct sites to modify. This is an important question, because accurate methylation deposition is critical for genome integrity and function, and alterations in methylation can result in abnormal developmental and pathological states, including cancers. The scientific outcome of this project could ultimately prove useful for developing novel technologies to correct methylation defects and thereby to improve agriculture and medicine. In addition, this project will provide many educational benefits, such as multi-disciplinary research training for undergraduate students, graduate students and postdocs, including those from underrepresented groups. The project will also engage high school students in research, with the aim of providing an enriching experience, particularly for women, minorities, and those who would be the first in their families to attend college. Another impact of the project will be the development of three learning modules centered on various aspects of genetics: tabletop science station for K-12 students, field trip module for middle school students, and summer science-camp for rural Wisconsin high school students and science teachers.
DNA methylation is not only prevalent in plants, fungi, and some animals, but also plays critical roles in genome defense, differentiation, development, disease, and environmental responses in these organisms. Despite its importance, remarkably little is known about the actual cue and the molecular mechanism that establish cell type- and locus-specific DNA methylation. Understanding the diverse functions of DNA methylation requires mechanistic knowledge of how DNA methyltransferase, the enzyme at the heart of this modification, is targeted to specific genomic loci. This project focuses on understanding the molecular actions of several new chromatin factors in mediating the establishment and maintenance of genome-wide and locus-specific DNA methylation patterns, using Arabidopsis thaliana as a powerful model. The comprehensive genetic, biochemical, and genomic studies proposed in this project will generate significant mechanistic insights into the specificity of DNA methylation regulation at the whole genome levels as well as local DNA sequence levels. Deep mechanistic knowledge of DNA methylation is crucial to understanding the molecular processes that establish DNA methylation landscapes under physiological and pathological conditions. This research will also have substantial impacts on understanding how DNA methylation is coordinated with other critical developmental, physiological, and environmental processes to regulate genome function in other plant and animal species.
