Title | Transcriptional coupling of distant regulatory genes in living embryos. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Levo, M, Raimundo, J, Bing, XYang, Sisco, Z, Batut, PJ, Ryabichko, S, Gregor, T, Levine, MS |
Journal | Nature |
Volume | 605 |
Issue | 7911 |
Pagination | 754-760 |
Date Published | 2022 05 |
ISSN | 1476-4687 |
Keywords | Animals, 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> |
DOI | 10.1038/s41586-022-04680-7 |
Alternate Journal | Nature |
PubMed ID | 35508662 |
Grant List | R01 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 |