Project Summary/Abstract
Epigenetic modifications regulate genome function. My research is focused on defining the
scope, mechanisms, and functional consequences of epigenome dynamics during development,
using the powerful genetic model system Arabidopsis thaliana. DNA methylation (5-
methylcytosine) is a heritable epigenetic mark associated with highly intertwined processes
including transcriptional gene silencing, transposable element (TE) repression, and regulation of
genomic imprinting. DNA methylation is concentrated in TEs to prevent their transcription and
proliferation, but this genome defense system comes at a potential cost – the methylation of
TEs or their remnants can inappropriately silence the transcription of proximal protein-coding
genes. Active DNA demethylation by 5-methylcytosine DNA glycosylases (also referred to as
DNA demethylases) functions to counteract DNA methyltransferases. But how these two
antagonistic activities are balanced to maintain the genome in a stable epigenetic state – where
transposable elements are kept methylated and silenced and genes are kept relatively free of
methylation and can be expressed – is a major question across eukaryotes and is one focus of
our current research. Our efforts in this area will significantly increase understanding of how the
activity of epigenetic pathways is modulated in response to the state of the epigenome and how
this information is integrated over cellular, developmental, and generational time scales.
Although epigenetic homeostasis appears to be a major force in the soma, developmentally-
regulated epigenetic reprogramming is essential for successful reproduction. DNA
demethylation in the female gamete establishes imprinted gene expression in a placenta-like
extra-embryonic seed tissue after fertilization. A critical unanswered question is how epigenetic
changes that are initiated by DNA demethylation are subsequently maintained, or not, when
maternal and paternal genomes are combined after fertilization and as cells take on distinct
identities. My laboratory applies diverse genetic, genomic, computational, and comparative
evolutionary approaches to address these fundamental questions in epigenetics.