Dynamic interplay between enhancer-promoter topology and gene activity. Author Hongtao Chen, Michal Levo, Lev Barinov, Miki Fujioka, James Jaynes, Thomas Gregor Publication Year 2018 Type Journal Article Abstract A long-standing question in gene regulation is how remote enhancers communicate with their target promoters, and specifically how chromatin topology dynamically relates to gene activation. Here, we combine genome editing and multi-color live imaging to simultaneously visualize physical enhancer-promoter interaction and transcription at the single-cell level in Drosophila embryos. By examining transcriptional activation of a reporter by the endogenous even-skipped enhancers, which are located 150 kb away, we identify three distinct topological conformation states and measure their transition kinetics. We show that sustained proximity of the enhancer to its target is required for activation. Transcription in turn affects the three-dimensional topology as it enhances the temporal stability of the proximal conformation and is associated with further spatial compaction. Furthermore, the facilitated long-range activation results in transcriptional competition at the locus, causing corresponding developmental defects. Our approach offers quantitative insight into the spatial and temporal determinants of long-range gene regulation and their implications for cellular fates. Keywords Animals, Drosophila, Promoter Regions, Genetic, Transcription, Genetic, Humans, Female, Male, Gene Expression Regulation, Developmental, Transcriptional Activation, Enhancer Elements, Genetic, Chromatin, Gene Editing Journal Nat Genet Volume 50 Issue 9 Pages 1296-1303 Date Published 2018 Sep ISSN Number 1546-1718 DOI 10.1038/s41588-018-0175-z Alternate Journal Nat Genet PMCID PMC6119122 PMID 30038397 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML