A novel promoter-tethering element regulates enhancer-driven gene expression at the bithorax complex in the Drosophila embryo

Development. 2008 Jan;135(1):123-31. doi: 10.1242/dev.010744. Epub 2007 Nov 28.


A key question in our understanding of the cis-regulation of gene expression during embryonic development has been the molecular mechanism that directs enhancers to specific promoters within a gene complex. Promoter competition and insulators are thought to play a role in regulating these interactions. In the bithorax complex of Drosophila, the IAB5 enhancer is located 55 kb 3' of the Abdominal-B (Abd-B) promoter and 48 kb 5' of the abdominal-A (abd-A) promoter. Although roughly equidistant from the two promoters, IAB5 specifically interacts only with the Abdominal-B promoter, even though the enhancer and promoter are separated by at least two insulators. Here we demonstrate that a 255 bp element, located 40 bp 5' of the Abd-B transcriptional start site, has a novel cis-regulatory activity as it is able to tether IAB5 to the Abd-B promoter in transgenic embryos. The tethering element is sufficient to direct IAB5 to an ectopic promoter in competition assays. Deletion of the promoter-tethering element results in the redirection of enhancer-driven gene expression on transgenes. Taken together, these results provide evidence that specific long-range enhancer-promoter interactions in the bithorax complex are regulated by a tethering element 5' of the Abd-B promoter. We discuss a bioinformatic analysis of the tethering element across different Drosophila species and a possible molecular mechanism by which this element functions. We also examine existing evidence that this novel class of cis-regulatory elements might regulate enhancer-promoter specificity at other gene complexes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Computational Biology
  • Drosophila Proteins / genetics*
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism*
  • Enhancer Elements, Genetic / genetics*
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Promoter Regions, Genetic / genetics*
  • Protein Binding


  • Drosophila Proteins
  • Homeodomain Proteins