"Epigenetic regulation of chromatin by the Keap1-Nrf2 xenobiotic response signaling in Drosophila"

University Of Minnesota Duluth, Duluth MN

Investigators

Linked publications, trials & patents

Abstract

ABSTRACT Conserved oxidative and xenobiotic response factors protect cells from damages caused by internal or external toxins. How these factors mediate the adaption to a constant exposure to environmental toxins is largely unclear. Epigenetic modifications are essential mechanisms that can fix the changes of transcription profiles in responses to constant environmental stimuli. Understanding the relationship between xenobiotic response factors and epigenetic machineries will help elucidate the mechanisms that mediate epigenetic and developmental adaptions to environmental toxins, and help understand the effects of environmental toxins to human health and diseases at the molecular level. The research in this proposal will focus on the interaction between the Keap1-Nrf2 signaling and the NURF chromatin remodeling complex. The Keap1-Nrf2 signaling pathway is essential for oxidative and xenobiotic responses, and is related with many diseases especially cancer. My laboratory employs Drosophila model system to assess the novel functions of the Keap1 and Nrf2 homologous proteins, dKeap1 and CncC. Our preliminary studies suggest a potential role of dKeap1 and CncC in the regulation of chromatin structure, as well as a potential interaction between dKeap1 and NURF. We hypothesize that dKeap1-CncC and NURF complexes can interact with each other and coordinate the regulation of chromatin structure and gene expression. In this proposal, our first aim is to determine the roles of dKeap1 and CncC in the establishment and maintenance of an opened chromatin structure. The second aim is to fully characterize the molecular interaction between dKeap1 and NURF both in vitro and in vivo. The proposed research is also expected to strengthen undergraduate education in both classroom and laboratory. The research aims can be divided into various sub-projects, which will either be introduced into undergraduate lab courses Molecular Biology Lab and Experimental Biology, or be used to support graduate thesis and undergraduate research in Deng laboratory. Through participating original research driven by hypothesis, students will acquire strong background and research experience on biomedical sciences. !