Areas of Interest
As data about the structure and content of the human genome accumulates, non-coding DNA regions have increasingly been revealed to play a central role in regulating gene expression. Through intricate, coordinated interactions, these elements control the specific spatiotemporal expression required for complex cell developmental programs. While positive regulatory elements such as enhancers have been abundantly characterized, negative regulatory elements such as silencers and enhancer blockers remain under-studied. My research aims to use a reporter assay, developed by the Boyle lab specifically for testing negative regulatory element (NRE) activity using a positive signal readout, in order to identify and characterize the activity of all silencers and enhancer blockers regulating a single gene. Additionally, my work focuses on understanding interactions between multiple positive and negative elements regulating the same target gene. By leveraging the flexibility of the NRE reporter construct and our matched positive regulatory element assay, I can test combinatorial effects of paired enhancers, promoters, enhancer blockers and silencers on gene expression, recapitulating the complexity of regulatory systems which control expression in a native context.