Conserved enhancer logic controls the notochord expression of vertebrate Brachyury
Kemmler, C. L.; Smolikova, J.; Moran, H. R.; Mannion, B. J.; Knapp, D.; Lim, F.; Czarkwiani, A.; Hermosilla Aguayo, V.; Rapp, V.; Fitch, O. E.; Boetschi, S.; Selleri, L.; Farley, E.; Braasch, I.; Yun, M.; Visel, A.; Osterwalder, M.; Mosimann, C.; Kozmik, Z.; Burger, A.
Show abstract
The cell type-specific expression of key transcription factors is central to development. Brachyury/T/TBXT is a major transcription factor for gastrulation, tailbud patterning, and notochord formation; however, how its expression is controlled in the mammalian notochord has remained elusive. Here, we identify the complement of notochord-specific enhancers in the mammalian Brachyury/T/TBXT gene. Using transgenic assays in zebrafish, axolotl, and mouse, we discover three Brachyury-controlling notochord enhancers T3, C, and I in human, mouse, and marsupial genomes. Acting as Brachyury-responsive, auto-regulatory shadow enhancers, deletion of all three enhancers in mouse abolishes Brachyury/T expression selectively in the notochord, causing specific trunk and neural tube defects without gastrulation or tailbud defects. Sequence and functional conservation of Brachyury-driving notochord enhancers with the brachyury/tbxtb loci from diverse lineages of fishes dates their origin to the last common ancestor of jawed vertebrates. Our data define the enhancers for Brachyury/T/TBXTB notochord expression as ancient mechanism in axis development.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Sox17 and β-catenin co-occupy Wnt-responsive enhancers to govern the endodermal gene regulatory network 97%
- TBX5 drives Aldh1a2 expression to regulate a RA-Hedgehog-Wnt gene regulatory network coordinating cardiopulmonary development 97%
- Gli3 utilizes Hand2 to synergistically regulate tissue-specific transcriptional networks 96%
Similar papers in this journal
Similar papers in this journal
- The anterior Hox gene ceh-13 and elt-1/GATA activate the posterior Hox genes nob-1 and php-3 to specify posterior lineages in the C. elegans embryo 96%
- HOX paralogs selectively convert binding of ubiquitous transcription factors into tissue-specific patterns of enhancer activation 95%
- Ciona Brachyury proximal and distal enhancers have different FGF dose-response relationships 95%
Similar papers in this journal
- Context-Dependent Enhancer Function Revealed Bytargeted Inter-Tad Relocation 97%
- Characterising open chromatin identifies novel cis-regulatory elements important for paraxial mesoderm formation and axis extension 97%
- Rapid and Quantitative Functional Interrogation of Human Enhancer Variant Activity in Live Mice 97%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.