UC Berkeley

Recent advances in live imaging technologies as well as non-equilibrium models are revealing new insights into the dynamic process of transcriptional regulation. The works described here all utilize MS2 imaging of transcription in live, developing embryo of fruit flies and zebrafish to investigate transcriptional dynamics in these model organisms. We utilize the resulting high resolution data to develop and test physics-based models of transcription.

We investigate two different regulatory enhancers in fruit fly embryos in three different projects. Through the first of these projects, we illuminate new information about the timing of transcriptional onset and the role of the pioneer-like factor Zelda. We connect newly discovered Zelda-dependent “hubs” of an activating transcription factor to transcriptionaloutput for the first time. Next, we undertake a systematic dissection of transcriptional regulation in eukaryotes. Through this project, we challenge the standard equilibrium model of transcriptional regulation and demonstrate the need for non-equilibrium models. We propose a model of transcription that incorporates transient transcription factor dynamics to drive DNA accessibility. The third project extends the study of transcriptional dynamics beyond initiation. We devise a novel experimental and theoretical foundation for the study of the interconnected regulation of the entire transcription cycle. In the last project we describe here, we move beyond the Drosophila field and expand our MS2 technology to zebrafish and established a transgenic MS2 reporter line of fish for the first time.

The imaging technology and modeling used in these projects have already proven to be incredibly useful for studying the dynamic process of transcription, revealing new mechanisms of regulation as well as enabling the development and testing of new theoretical models of transcription. This is just the beginning and, in the coming years, further improvements in imaging technologies in combination with continued efforts on the theoretical modeling frontwill surely continue to bring about new discoveries in the field of transcriptional regulation.