My research focuses on understanding the mechanisms establishing and regulating epigenetic information, and how epigenetic systems ultimately contribute to gene regulation, disease, and other phenotypes. In addition to the genetic information encoded within the DNA, other forms of information exist in the cell. Epigenetic information is heritable, affects gene expression states and phenotypes, but is independent of DNA sequence. Examples of epigenetic systems include DNA methylation, histone modifications, and chromatin structure. These epigenetic systems play vital roles in gene regulation, and defects in epigenetic regulation have been implicated in a variety of human diseases including cancer. My lab uses the fruit fly Drosophila melanogaster as a model system to investigate epigenetic systems and their influence on development and gene regulation. Currently, there are three on-going projects in the lab:
The HP1 protein family: Heterochromatin protein 1a (HP1a) was discovered as the first heterochromatin-associated protein. Its binding characterizes the heterochromatic regions of the fly genome, and homologs have been identified in species ranging from yeast to humans. The HP1a protein contains two conserved domains, the chromo domain, and the chromo-shadow domain. Based on this domain structure, four additional HP1 family proteins have been identified in Drosophila melanogaster. Of these, HP1B and HP1C, like HP1a, are ubiquitously expressed, while HP1D/RHINO and HP1E are restricted to the germline in females and males respectively. While HP1a binds large domains in heterochromatin, it also shows binding to active transcription start sites, where it is generally found in the company of HP1B and/or HP1C. We are using molecular genetic and genomics approaches to understand the relationship between HP1a, HP1B, and HP1C, and their effect on gene regulation.
The role of epigenetics in exercise response: Exercise is a common form of treatment recommended to combat the increasing obesity problem observed in many countries. How individuals respond to exercise is highly variable, and the source of this variation is not well understood. We are using the fruit fly Drosophila melanogaster as a model for exercise biology. Taking advantage of the genetics resources available in Drosophila, our experiments are designed to determine the relative importance of genetics and epigenetics in generating the variability in exercise response.
The regulation of H3K9 methylation: H3K9 methylation is a histone mark generally associated with silent regions of the genome and heterochromatin. In many eukaryotes including Drosophila, H3K9 methylation is generated by three classes of SET domain containing histone methyltransferases. In Drosophila, the action of SU(VAR)3-9, EGG, and G9a produces the genome-wide H3K9 methylation patters. However, how the three enzymes are coordinated and what their individual roles are is poorly understood. We are using molecular genetic, biochemical, and genomics approaches to answer these questions.
Epigenetics and chromatin
