Global Quantitative Mapping of Silencer Activity in Drosophila Cells
Silencers are important regulatory elements for the precise control of eukaryotic gene expression. Global unbiased assessment of silencer activity has not been reported. Here we present LOSTRES (loss of self-transcribing regulatory element signal sequencing) to measure the repressing activity of millions of DNA candidates in parallel. Thousands of silencers were identified in Drosophila genome. Combined activities of gene-proximal silencers and enhancers correlate positively with gene expression levels. At endogenous genomic loci, silencers differ from enhancers in epigenetic features and are devoid of most enhancer-bound proteins. In sum, our results provide a function-based, unbiased silencer identification method, reveal complexity in silencer identity, and shed light into the functional mechanism of silencers. Overall design: Silencer identification in Drosophila melanogaster.