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

61 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

Fingerprint

Dive into the research topics of 'Transcriptional coupling of distant regulatory genes in living embryos'. Together they form a unique fingerprint.

Cite this