27 December 2019
Predicting how the gene expression patterns that specify animal body plans arise from interactions between transcription factor proteins and regulatory DNA remains a major challenge in physical biology. We utilize live imaging and theoretical approaches to examine how transcriptional control at the single-cell level gives rise to a sharp stripe of cytoplasmic mRNA in the fruit fly embryo. While the modulation of transcriptional bursting has been implicated as the primary lever for controlling gene expression, we find that this alone cannot quantitatively recapitulate pattern formation. Instead, we find that the pattern arises through the joint action of 2 regulatory strategies—control of bursting and control of the total duration of transcription—that originate from distinct underlying molecular mechanisms.
Predicting how interactions between transcription factors and regulatory DNA sequence dictate rates of transcription and, ultimately, drive developmental outcomes remains an open challenge in physical biology. Using stripe 2 of the even-skipped gene in Drosophila embryos as a case study, we dissect the regulatory forces underpinning a key step along the developmental decision-making cascade: the generation of cytoplasmic mRNA patterns via the control of transcription in individual cells. Using live imaging and computational approaches, we found that the transcriptional burst frequency is modulated across the stripe to control the mRNA production rate. However, we discovered that bursting alone cannot quantitatively recapitulate the formation of the stripe and that control of the window of time over which each nucleus transcribes even-skipped plays a critical role in stripe formation. Theoretical modeling revealed that these regulatory strategies (bursting and the time window) respond in different ways to input transcription factor concentrations, suggesting that the stripe is shaped by the interplay of 2 distinct underlying molecular processes.