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.
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