Large distances separate coregulated genes in living Drosophila embryos

Tyler Heist, Takashi Fukaya, Michael Levine

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)15062-15067
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number30
DOIs
StatePublished - 2019

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Drosophila embryos
  • Enhancers
  • Live-imaging
  • Transcription
  • Transvection

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