|
| Status |
Public on Feb 01, 2022 |
| Title |
Transcriptional Coupling of Distant Regulatory Genes in Living Embryos |
| Organism |
Drosophila melanogaster |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Other
|
| Summary |
The prevailing view of metazoan gene regulation is that individual genes are independently regulated by their own dedicated sets of transcriptional enhancers. Past studies reported long-range gene-gene associations, but their functional significance in regulating transcription remains uncertain and controversial. Here we employ quantitative single cell live imaging methods to provide the first demonstration of co-dependent transcriptional dynamics of genes separated by large genomic distances in living embryos. We find extensive physical and functional associations of distant paralogous genes, including co-regulation by shared enhancers and co-transcriptional bursting over distances of nearly 250kb. Regulatory inter-connectivity 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 of distant genes throughout the Drosophila genome underlies a broad spectrum of conserved developmental processes, suggesting a general strategy for long-range integration of gene activities.
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| Overall design |
MicroC experiments were conducted in biological duplicates. The control line was yw. Experimental lines were CRISPR-mediated deletions of specific architectural elements. All experiments were conducted with embryos at the nc14 stage.
|
| Web link |
https://doi.org/10.1038/s41586-022-04680-7
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| |
|
| Contributor(s) |
Bing X, Levo M, Raimundo J, Levine M |
| Citation(s) |
35508662 |
| |
| Submission date |
Apr 28, 2021 |
| Last update date |
May 27, 2022 |
| Contact name |
Mike Levine |
| E-mail(s) |
msl2@princeton.edu
|
| Organization name |
Princeton University
|
| Department |
Lewis Sigler Institute
|
| Street address |
South Dr
|
| City |
Princeton |
| State/province |
NJ |
| ZIP/Postal code |
08540 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL25244 |
Illumina NovaSeq 6000 (Drosophila melanogaster) |
|
| Samples (14)
|
| GSM5269157 |
Additional control - for extra genomic coverage-replicate1 |
| GSM5269158 |
Additional control - for extra genomic coverage-replicate2 |
| GSM5269159 |
knrl/kni - knrl extended tethers replacement1 |
|
| Relations |
| BioProject |
PRJNA725880 |
| SRA |
SRP316764 |
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