Multilayered Mechanisms for Long-range Regulatory Interactions in Eukaryotic Transcription

Transcription is a fundamental biological reaction that underlies essentially all developmental and physiological processes across species. While substantial efforts have been made to decipher the basic mechanisms of transcriptional regulation over the decades, we are still far from a comprehensive understanding of this highly intricate biological reaction including the temporal and spatial dynamics of the process. In recent years, new concepts and models have been proposed based on novel insights obtained from the use of cutting-edge technologies such as genome-editing, whole-genome assays, structural analysis, and quantitative live-imaging approaches. In this review, I summarize emerging models and concepts for the dynamic modulation of long-range regulatory interactions in the context of animal development. I suggest that the multilayered actions of enhancers and associating regulatory DNAs such as"Facilitators" and "Range Extenders" dynamically modulate clustering of transcription machineries at specific genomic loci to flexibly control the temporal and spatial dynamics of gene expression during development.