We are working to elucidate the fundamental mechanisms of transcriptional regulation during animal development. Regulatory DNAs called enhancers play a central role in controlling the temporal and spatial specificity of gene expression in response to intrinsic and extrinsic signals. It is estimated that more than 900,000 enhancers are embedded in the human genome, suggesting that a typical human gene is regulated by ~40-50 enhancers. Increasing number of evidence suggests that the diversification of enhancer functions plays a critical role in producing the phenotypic complexities of higher eukaryotes during evolution. However, the fundamental question namely "How do enhancers control transcription dynamics at the molecular level?" remains as an outstanding question in modern biology. Using the early Drosophila embryo as a model, we aim to understand the fundamental principles of enhancer function by utilizing a wide range of techniques, including live-imaging, super-resolution microscopy, genome-editing, biochemistry, and quantitative image analysis.

Understanding the molecular mechanism of enhancer-promoter communication

The functions of enhancers are highly regulated through the formation of 3D genomic structures such as topologically associating domains (TADs) and tethering loops. It has also been suggested that non-coding RNAs, such as enhancer RNAs, play an important role in controlling enhancer function. More recently, increasing evidence suggests that many transcriptional regulators and RNA polymerase II undergo dynamic condensate formation in living cells. By combining live-imaging/super-resolution methods with a variety of computational and genome-engineering approaches, we aim to obtain comprehensive understanding of the basic mechanisms of enhancer-promoter communication during animal development.

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