Karolinska Institutet Research Lectures: Michael S. Levine
Title: “Visualization and evolution of transcriptional enhancers in animal development”.
Michael S. Levine, Professor of Molecular Biology, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA
Transcriptional enhancers are short segments of DNA that switch genes on and off in response to a variety of intrinsic and external signals. During the past two years we have used newly developed quantitative live imaging methods to visualize the activities of defined developmental enhancers in the early Drosophila embryo. The eve stripe 2 enhancer produces a highly dynamic pattern of de novo transcription that persists for just 10-15 minutes after formation of the mature stripe. It is possible that these dynamics are fostered by transcriptional bursts. I will discuss evidence that the regulation of bursting frequency is a key determinant of gene control in development. Moreover, the use of a 2-color detection system provides evidence that a single enhancer can co-activate two linked reporter genes. This observation challenges traditional models of enhancer-promoter looping. I will also discuss evidence that developmental enhancers are “suboptimized”. They contain weak binding motifs and suboptimal spacing between adjacent sites. Optimization of binding affinities and syntax cause strong but nonspecific patterns of gene expression in development.