A chromatin insulator mediates transgene homing and very long-range enhancer-promoter communication

Development. 2009 Sep;136(18):3077-87. doi: 10.1242/dev.036467. Epub 2009 Aug 12.


Insulator sequences help to organize the genome into discrete functional regions by preventing inappropriate cross-regulation. This is thought to be mediated in part through associations with other insulators located elsewhere in the genome. Enhancers that normally drive Drosophila even skipped (eve) expression are located closer to the TER94 transcription start site than to that of eve. We discovered that the region between these genes has enhancer-blocking activity, and that this insulator region also mediates homing of P-element transgenes to the eve-TER94 genomic neighborhood. Localization of these activities to within 0.6 kb failed to separate them. Importantly, homed transgenic promoters respond to endogenous eve enhancers from great distances, and this long-range communication depends on the homing/insulator region, which we call Homie. We also find that the eve promoter contributes to long-distance communication. However, even the basal hsp70 promoter can communicate with eve enhancers across distances of several megabases, when the communication is mediated by Homie. These studies show that, while Homie blocks enhancer-promoter communication at short range, it facilitates long-range communication between distant genomic regions, possibly by organizing a large chromosomal loop between endogenous and transgenic Homies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chromatin / genetics*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics*
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Promoter Regions, Genetic*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transgenes*
  • Valosin Containing Protein


  • Cell Cycle Proteins
  • Chromatin
  • Drosophila Proteins
  • Homeodomain Proteins
  • Transcription Factors
  • eve protein, Drosophila
  • Valosin Containing Protein
  • ter94 protein, Drosophila