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

Large distances separate coregulated genes in living Drosophila embryos.

Author information

1
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544.
2
Institute for Quantitative Biosciences, The University of Tokyo, 113-0032 Tokyo, Japan.
3
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 113-0032 Tokyo, Japan.
4
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544; msl2@princeton.edu.
5
Department of Molecular Biology, Princeton University, Princeton, NJ 08544.

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.

KEYWORDS:

Drosophila embryos; enhancers; live-imaging; transcription; transvection

PMID:
31285341
PMCID:
PMC6660726
[Available on 2020-01-08]
DOI:
10.1073/pnas.1908962116

Conflict of interest statement

The authors declare no conflict of interest.

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