Large distances separate coregulated genes in living embryos. Author Tyler Heist, Takashi Fukaya, Michael Levine Publication Year 2019 Type Journal Article 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 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. Journal Proc Natl Acad Sci U S A Volume 116 Issue 30 Pages 15062-15067 Date Published 07/2019 ISSN Number 1091-6490 DOI 10.1073/pnas.1908962116 Alternate Journal Proc. Natl. Acad. Sci. U.S.A. PMCID PMC6660726 PMID 31285341 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML