Dynamic interplay between non-coding enhancer transcription and gene activity in development

Abstract

Non-coding transcription at the intergenic regulatory regions is a prevalent feature of metazoan genomes, but its biological function remains uncertain. Here, we devised a live-imaging system that permits simultaneous visualization of gene activity along with intergenic non-coding transcription at the single-cell resolution in Drosophila. Quantitative image analysis revealed that elongation of RNA polymerase II across the internal core region of enhancers leads to suppression of transcriptional bursting from linked genes. Super-resolution imaging and genome-editing analysis further demonstrated that enhancer transcription antagonizes molecular crowding of transcription factors, thereby interrupting the formation of transcription hub at the gene locus. We also show that a certain class of developmental enhancers are structurally optimized to co-activate gene transcription together with non-coding transcription effectively. We suggest that enhancer function is flexibly tunable through the modulation of hub formation via surrounding non-coding transcription during development.

Transcriptional clusters follow a conserved condensation-dispersal sequence during stem cell differentiation

“…In embryonic development, persistent enhancer hubs were found to be visited by different genes depending on differentiation and transcriptional activation [84,85]. According transient interactions of genes with enhancers that control their transcription has been seen in live imaging [86,87] as well as pseudo-time reconstruction from fixed cells [31]. Hubs involving enhancers and genes also form prior to transcriptional activation, with an involvement of recruited Pol II, seemingly providing a configuration that is poised for subsequent transcriptional activation during differentiation processes ( [88,89,37]).…”