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| Status |
Public on Sep 29, 2022 |
| Title |
Promoter repression and 3D-restructuring resolves divergent developmental gene expression in TADs [Hi-C] |
| Organisms |
Gallus gallus; Mus musculus; Monodelphis domestica |
| Experiment type |
Other
|
| Summary |
Cohesin loop extrusion facilitates precise gene expression by continuously driving promoters to sample all enhancers located within the same topologically-associated domain (TAD). However, many TADs contain multiple genes with divergent expression patterns, thereby indicating additional forces further refine how enhancer activities are utilised. Here, we unravel the mechanisms enabling a new gene, Rex1, to emerge with divergent expression within the ancient Fat1 TAD in placental mammals. We show that such divergent expression is not determined by a strict enhancer-promoter compatibility code, intra-TAD position or nuclear envelope-attachment. Instead, TAD-restructuring in embryonic stem cells (ESCs) separates Rex1 and Fat1 with distinct proximal enhancers that independently drive their expression. By contrast, in later embryonic tissues, DNA methylation renders the inactive Rex1 promoter profoundly unresponsive to Fat1 enhancers within the intact TAD. Combined, these features adapted an ancient regulatory landscape during evolution to support two entirely independent Rex1 and Fat1 expression programs. Thus, rather than operating only as rigid blocks of co-regulated genes, TAD-regulatory landscapes can orchestrate complex divergent expression patterns in evolution.
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| Overall design |
We employed HiC to embryonic limbs from stage-matched chicken and opossum embryos to map alterations to 3D chromatin structure across evolution.
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| Contributor(s) |
Robson MI, Ringel AR |
| Citation missing |
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| |
| Submission date |
Oct 12, 2021 |
| Last update date |
Oct 02, 2022 |
| Contact name |
Michael I Robson |
| E-mail(s) |
robson@molgen.mpg.de
|
| Organization name |
Max Planck Institute for Molecular Genetics
|
| Street address |
Max Planck Institut für molekulare Genet, Ihnestrasse 63-73
|
| City |
Berlin |
| ZIP/Postal code |
14195 |
| Country |
Germany |
| |
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| Platforms (3) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL26853 |
Illumina NovaSeq 6000 (Gallus gallus) |
| GPL30856 |
Illumina NovaSeq 6000 (Monodelphis domestica) |
|
| Samples (6)
|
| GSM6482918 |
cHiC__ESC_G4_deltaPromoterRex1-Triml_mouse_Rep-1 |
| GSM6482919 |
cHiC__ESC_G4_deltaPromoterRex1_mouse_Rep-1 |
| GSM6482920 |
cHiC_ limb_E115_deltaD1_mouse_Rep-1 |
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| This SubSeries is part of SuperSeries: |
| GSE185775 |
Repression and 3D-restructuring resolves regulatory conflicts in evolutionarily rearranged genomes |
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| Relations |
| BioProject |
PRJNA770713 |
| SRA |
SRP341076 |
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