Conserved enhancers control notochord expression of vertebrate Brachyury.

0578356 - ÚMG 2024 RIV US eng J - Journal Article
Kemmler, C. L. - Smolíková, Jana - Moran, H. R. - Mannion, B. J. - Knapp, D. - Lim, F. - Czarkwiani, A. - Aguayo, V. H. - Rapp, V. - Fitch, O. E. - Botschi, S. - Selleri, L. - Farley, E. - Braasch, I. - Yun, M. - Visel, A. - Osterwalder, M. - Mosimann, C. - Kozmik, Zbyněk - Burger, A.
Conserved enhancers control notochord expression of vertebrate Brachyury.
Nature Communications. Roč. 14, č. 1 (2023), s. 6594. E-ISSN 2041-1723
R&D Projects: GA MŠMT(CZ) LM2018126; GA MŠMT ED2.1.00/19.0395; GA MŠMT(CZ) ED1.1.00/02.0109; GA ČR GA23-07056S
Institutional support: RVO:68378050
Keywords : transcription factors * Brachyury/T/TBXT * notochord expression
OECD category: Biochemistry and molecular biology
Impact factor: 16.6, year: 2022
Method of publishing: Open access
https://www.nature.com/articles/s41467-023-42151-3

The cell type-specific expression of key transcription factors is central to development and disease. 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 conserved Brachyury-controlling notochord enhancers, T3, C, and I, in human, mouse, and marsupial genomes. Acting as Brachyury-responsive, auto-regulatory shadow enhancers, in cis deletion of all three enhancers in mouse abolishes Brachyury/T/Tbxt expression selectively in the notochord, causing specific trunk and neural tube defects without gastrulation or tailbud defects. The three Brachyury-driving notochord enhancers are conserved beyond mammals in the brachyury/tbxtb loci of fishes, dating their origin to the last common ancestor of jawed vertebrates. Our data define the vertebrate enhancers for Brachyury/T/TBXTB notochord expression through an auto-regulatory mechanism that conveys robustness and adaptability as ancient basis for axis development.
Permanent Link: https://hdl.handle.net/11104/0347411