Transcriptional coupling of distant regulatory genes in living embryos.

TitleTranscriptional coupling of distant regulatory genes in living embryos.
Publication TypeJournal Article
Year of Publication2022
AuthorsLevo, M, Raimundo, J, Bing, XYang, Sisco, Z, Batut, PJ, Ryabichko, S, Gregor, T, Levine, MS
JournalNature
Volume605
Issue7911
Pagination754-760
Date Published2022 May
ISSN1476-4687
KeywordsAnimals, Drosophila, Embryonic Development, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Genes, Regulator, Genome, Promoter Regions, Genetic, Single-Cell Analysis, Transcription, Genetic
Abstract

<p>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 associations, 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.</p>

DOI10.1038/s41586-022-04680-7
Alternate JournalNature
PubMed ID35508662
PubMed Central ID3339270
Grant ListR01 GM097275 / GM / NIGMS NIH HHS / United States
U01 DA047730 / DA / NIDA NIH HHS / United States
U01 DK127429 / DK / NIDDK NIH HHS / United States
U01 EB021239 / EB / NIBIB NIH HHS / United States
R35 GM118147 / GM / NIGMS NIH HHS / United States