Enhancer-core-promoter specificity separatesdevelopmental and housekeeping generegulation

摘要

Gene transcription in animals involves the assembly of RNA polymerase II at core promoters and its cell type-specific activation by enhancers that can be located more distally. However, how ubiquitous expression of housekeeping genes is achieved has remained less clear. In particular, it is unknown whether ubiquitously active enhancers exist and how developmental and housekeeping gene regulation is separated. An attractive hypothesis is that different core promoters might exhibit an intrinsic specificity towards certain enhancers^–. This is conceivable as different core promoter sequence elements are differentially distributed between genes of different functions, including elements that are predominantly at developmentally regulated or housekeeping genes, respectively^–. Here, we show that thousands of enhancers in Drosophila melanogaster S2 cells and ovarian somatic cells (OSCs) exhibit a markedspecificity towards one of two core promoters – onederived from a ubiquitously expressed ribosomal protein geneand another from a developmentally regulated transcriptionfactor (TF) – and confirm the existence of these twoclasses for five additional core promoters from genes withdiverse functions. Housekeeping enhancers are active acrossthe two cell types, while developmental enhancers exhibitstrong cell type specificity. Both enhancer classes differin their genomic distribution, the functions of neighbouringgenes, and these genes’ core promoter elements. Inaddition, we identify two TFs – DREF and Trl/GAGA– that bind and activate housekeeping versusdevelopmental enhancers, respectively. Our results provideevidence for a sequence-encoded enhancer-core promoterspecificity that separates developmental and housekeepinggene regulatory programs for thousands of enhancers andtheir target genes across the entire genome.