Abstract
The development of the precellular Drosophila embryo is characterized by exceptionally rapid transitions in gene activity, with broadly distributed maternal regulatory gradients giving way to precise on/off patterns of gene expression within a one-hour window, between two and three hours after fertilization [1]. Transcriptional repression plays a pivotal role in this process, delineating sharp expression patterns (e.g., pair-rule stripes) within broad domains of gene activation. As many as 20 different sequence-specific repressors have been implicated in this process, yet the mechanisms by which they silence gene expression have remained elusive [2]. Here we report the development of a method for the quantitative visualization of transcriptional repression. We focus on the Snail repressor, which establishes the boundary between the presumptive mesoderm and neurogenic ectoderm [3]. We find that elongating Pol II complexes complete transcription after the onset of Snail repression. As a result, moderately sized genes (e.g., the 22 kb sog locus) are fully silenced only after tens of minutes of repression. We propose that this "repression lag" imposes a severe constraint on the regulatory dynamics of embryonic patterning and further suggest that posttranscriptional regulators, like microRNAs, are required to inhibit unwanted transcripts produced during protracted periods of gene silencing.