Genetic and molecular studies of DNA methylation and its role in the control of gene expression throughout development.
We are interested in cell memory, or the process by which dividing cells inherit states of gene activity. In particular, our work focuses on an epigenetic modification of DNA called cytosine methylation. We are using Arabidopsis thaliana as a model genetic system to study the cytosine methylation pathway, and its role in gene regulation throughout development. The long term goal of this work is to understand the function of all of the genes in the methylation pathway, and to understand how they function together to promote proper methylation patterning. Another major goal is to understand the mechanisms by which methylation regulates genes during development.
Our work stems from the discovery of a series of hypermethylated SUPERMAN (SUP) epigenetic alleles in Arabidopsis (Science 277, 1100-1103). These unstable alleles are associated with dense methylation of the promoter and coding regions of the SUP gene and accompanied by a decreased level of SUP RNA. We also find that a number of Arabidopsis mutants which decrease cytosine methylation, surprisingly, give rise to new hypermethylated sup alleles. This is superficially similar to a phenomenon found in many mammalian cancer cells which show overall genomic demethylation coupled with hypermethylation of specific tumor suppressor genes.
We are now studying the exact nature of the methylation defects at SUPERMAN, and at another gene involved in floral development called AGAMOUS. We are also using genetic screens and various biochemical approaches to isolate and study new genes involved in the control of DNA methylation. This includes our ongoing characterization of a new family of putative de novo DNA methyltransferases.