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© Melody Merle
Fluorescently labeled five day old gastruloid, a mouse embryonic stem-cell derived pseudo-embryo.
Publication : Nature

Transcriptional coupling of distant regulatory genes in living embryos.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature - 01 May 2022

Levo M, Raimundo J, Bing XY, Sisco Z, Batut PJ, Ryabichko S, Gregor T, Levine MS,

Link to Pubmed [PMID] – 35508662

Link to DOI – 10.1038/s41586-022-04680-7

Nature 2022 05; 605(7911): 754-760

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.

https://pubmed.ncbi.nlm.nih.gov/35508662