Transcriptional coupling of distant regulatory genes in living embryos

Michal Levo, João Raimundo, Xin Yang Bing, Zachary Sisco, Philippe J. Batut, Sergey Ryabichko, Thomas Gregor, Michael S. Levine

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The prevailing view of metazoan gene regulation is that individual genes are independently regulated by their own dedicated sets of transcriptional enhancers. Past studies have reported long-range gene–gene associations1–3, but their functional importance in regulating transcription remains unclear. Here we used quantitative single-cell live imaging methods to provide a demonstration of co-dependent transcriptional dynamics of genes separated by large genomic distances in living Drosophila embryos. We find extensive physical and functional associations of distant paralogous genes, including co-regulation by shared enhancers and co-transcriptional initiation over distances of nearly 250 kilobases. Regulatory interconnectivity depends on promoter-proximal tethering elements, and perturbations in these elements uncouple transcription and alter the bursting dynamics of distant genes, suggesting a role of genome topology in the formation and stability of co-transcriptional hubs. Transcriptional coupling is detected throughout the fly genome and encompasses a broad spectrum of conserved developmental processes, suggesting a general strategy for long-range integration of gene activity.

Original languageEnglish (US)
Pages (from-to)754-760
Number of pages7
JournalNature
Volume605
Issue number7911
DOIs
StatePublished - May 26 2022

All Science Journal Classification (ASJC) codes

  • General

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