Dissecting the dynamics of coordinated active transcriptional repression in a multicellular organism

Abstract

AbstractThe ability to refine transcriptional levels via active repression in an euchromatic context represents a critical regulatory process during development. While the molecular players of active repression are well described, their dynamics remain largely obscure. By monitoring expression dynamics of the pro-EMT developmental genesnailinDrosophilaembryos, we uncovered and quantified the timescale of kinetic bottlenecks tuning transcription during repression. Repression is associated with the transition of the promoter from two states to a three-state regime, comprising two temporally distinct inactive periods. Surprisingly, repression occurs without abrupt changes in Pol II initiation rates. By monitoring nuclear Sna protein levels, we show that Sna-mediated repression operates with high cooperativity, a feature dictating the degree of cell-cell coordination in the imposition of repression. Our approach offers quantitative insights into the dynamics of repression mediated by short-range repressors and how their cooperativity may coordinate cell fate decisions within a tissue.