Regulation of spatiotemporal limits of developmental gene expression via enhancer grammar

• DOI: 10.1073/pnas.1917040117
• Publication Date: 2020-06-16T00:26:40Z
• Authors: Samuel H. Keller; Siddhartha G. Jena; Yuji Yamazaki; Bomyi Lim
• Keywords: Enhancer RNAs

The regulatory specificity of a gene is determined by the structure its enhancers, which contain multiple transcription factor binding sites. A unique combination sites in an enhancer determines boundary target expression, and their disruption often leads to developmental defects. Despite extensive characterization motifs enhancer, it still unclear how each site contributes overall transcriptional activity. Using live imaging, quantitative analysis, mathematical modeling, we measured contribution individual regulation. We show that arrangement within Rho-GTPase component t48 mediates expression mainly regulating timing activation along dorsoventral axis Drosophila embryos. By tuning affinity Dorsal (Dl) Zelda (Zld) sites, single modulations are sufficient induce significant changes transcription. Yet, no one seems have dominant role; rather, synergistically drive increases Interestingly, Dl Zld demonstrate distinct roles change spatial boundaries , mostly affecting bursting frequency rather than amplitude or duration. However, modulating for pioneer affects both amplitude, suggesting may potentiate higher recruitment DNAs. propose such fine-tuning dynamic control via play important role ensuring normal development.