Enhancer-core-promoter specificity separates developmental and housekeeping gene regulation

Nature. 2015 Feb 26;518(7540):556-9. doi: 10.1038/nature13994. Epub 2014 Dec 15.


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 been 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 to certain enhancers. This is conceivable, as various core promoter sequence elements are differentially distributed between genes of different functions, including elements that are predominantly found at either developmentally regulated or at housekeeping genes. Here we show that thousands of enhancers in Drosophila melanogaster S2 and ovarian somatic cells (OSCs) exhibit a marked specificity to one of two core promoters--one derived from a ubiquitously expressed ribosomal protein gene and another from a developmentally regulated transcription factor--and confirm the existence of these two classes for five additional core promoters from genes with diverse functions. Housekeeping enhancers are active across the two cell types, while developmental enhancers exhibit strong cell-type specificity. Both enhancer classes differ in their genomic distribution, the functions of neighbouring genes, and the core promoter elements of these neighbouring genes. In addition, we identify two transcription factors--Dref and Trl--that bind and activate housekeeping versus developmental enhancers, respectively. Our results provide evidence for a sequence-encoded enhancer-core-promoter specificity that separates developmental and housekeeping gene regulatory programs for thousands of enhancers and their target genes across the entire genome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics*
  • Enhancer Elements, Genetic / genetics*
  • Gene Expression Regulation, Developmental / genetics*
  • Genes, Essential / genetics*
  • Genome, Insect / genetics
  • Models, Genetic
  • Organ Specificity
  • Promoter Regions, Genetic / genetics*
  • Substrate Specificity / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation / genetics


  • DNA-Binding Proteins
  • Dref protein, Drosophila
  • Drosophila Proteins
  • Transcription Factors
  • Trl protein, Drosophila

Associated data

  • GEO/GSE40739
  • GEO/GSE57876