Large distances separate coregulated genes in living Drosophila embryos

Proc Natl Acad Sci U S A. 2019 Jul 23;116(30):15062-15067. doi: 10.1073/pnas.1908962116. Epub 2019 Jul 8.


Transcriptional enhancers are short segments of DNA that switch genes on and off in response to a variety of cellular signals. Many enhancers map quite far from their target genes, on the order of tens or even hundreds of kilobases. There is extensive evidence that remote enhancers are brought into proximity with their target promoters via long-range looping interactions. However, the exact physical distances of these enhancer-promoter interactions remain uncertain. Here, we employ high-resolution imaging of living Drosophila embryos to visualize the distances separating linked genes that are coregulated by a shared enhancer. Cotransvection assays (linked genes on separate homologs) suggest a surprisingly large distance during transcriptional activity: at least 100-200 nm. Similar distances were observed when a shared enhancer was placed into close proximity with linked reporter genes in cis. These observations are consistent with the occurrence of "transcription hubs," whereby clusters (or condensates) of multiple RNA polymerase II complexes and associated cofactors are periodically recruited to active promoters. The dynamics of this process might be responsible for rapid fluctuations in the distances separating the transcription of coregulated reporter genes during transvection. We propose that enhancer-promoter communication depends on a combination of classical looping and linking models.

Keywords: Drosophila embryos; enhancers; live-imaging; transcription; transvection.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • Animals, Genetically Modified
  • Chromosomes, Insect / chemistry*
  • DNA-Directed RNA Polymerases / genetics
  • DNA-Directed RNA Polymerases / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism
  • Embryo, Nonmammalian
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation, Developmental*
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Lac Operon
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Models, Genetic*
  • Molecular Imaging
  • Promoter Regions, Genetic*
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • Snail Family Transcription Factors / genetics
  • Snail Family Transcription Factors / metabolism
  • Transcription, Genetic


  • Luminescent Proteins
  • Snail Family Transcription Factors
  • red fluorescent protein
  • sna protein, Drosophila
  • Green Fluorescent Proteins
  • MS2 polymerase
  • RNA Polymerase II
  • DNA-Directed RNA Polymerases