@article{c46b272adfc046fda2bc51d00d1a1f46,
title = "Transcriptional coupling of distant regulatory genes in living embryos",
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.",
author = "Michal Levo and Jo{\~a}o Raimundo and Bing, {Xin Yang} and Zachary Sisco and Batut, {Philippe J.} and Sergey Ryabichko and Thomas Gregor and Levine, {Michael S.}",
note = "Funding Information: We thank all of the members of the Levine and Gregor laboratories for discussions and comments on the manuscript; E. Wieschaus for suggestions at various stages of the project; M. J. Rowley for his assistance with the SIP algorithm that was used for the automatic detection of focal contacts; E. Gatzogiannis for his help with live imaging microscopy; and B. Zoller for his contribution to the imaging analysis pipeline. This work was supported in part by the US National Science Foundation, through the Center for the Physics of Biological Function (PHY-1734030), and by National Institutes of Health Grants R01GM097275 (to T.G.), U01DA047730 (to T.G. and M.S.L.) and U01DK127429 (to T.G. and M.S.L.). The work was also supported by National Institutes of Health grant R35 GM118147 (to M.S.L.). M.L. is the recipient of a Human Frontier Science Program fellowship (LT000852/2016-L), EMBO long-term postdoctoral fellowship (ALTF 1401-2015) and the Rothschild postdoctoral fellowship. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2022",
month = may,
day = "26",
doi = "10.1038/s41586-022-04680-7",
language = "English (US)",
volume = "605",
pages = "754--760",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7911",
}