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.

Project Narrative DNA methylation is an epigenetic mark crucial for maintaining transcriptional states and aberrant DNA methylation patterns are a hallmark of cancer and other diseases. This research will decipher how DNA methylation patterns are dynamically maintained from the cellular to generational scales, determine the function of DNA demethylation during somatic and reproductive development, and identify the mechanisms underlying imprinted gene expression. The research will lead to new understanding of how these processes are modulated during normal growth and development and how they are potentially altered in disease states.