TitleLarge distances separate coregulated genes in living embryos.
Publication TypeJournal Article
Year of Publication2019
AuthorsHeist, T, Fukaya, T, Levine, M
JournalProc Natl Acad Sci U S A
Date Published2019 Jul 23

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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID31285341
PubMed Central IDPMC6660726
Grant ListR35 GM118147 / GM / NIGMS NIH HHS / United States