{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Kemmler CL"],"funding":["Swiss National Science Foundation","NIDCR NIH HHS","NIDDK NIH HHS","NHLBI NIH HHS","NHGRI NIH HHS","NIGMS NIH HHS"],"pubmed_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 <i>Brachyury/T/TBXT</i> gene. Using transgenic assays in zebrafish, axolotl, and mouse, we discover three <i>Brachyury</i>-controlling notochord enhancers <i>T3</i>, <i>C</i>, and <i>I</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 <i>Brachyury</i>-driving notochord enhancers with the <i>brachyury/tbxtb</i> loci from diverse lineages of fishes dates their origin to the last common ancestor of jawed vertebrates. Our data define the enhancers for <i>Brachyury/T/TBXTB</i> notochord expression as ancient mechanism in axis development."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2023.04.20.536761"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10153258"],"repository":["biostudies-literature"],"pubmed_title":["Conserved enhancer logic controls the notochord expression of vertebrate <i>Brachyury</i>."],"pmcid":["PMC10153258"],"funding_grant_id":["R01 DE024745","DP2 HG010013","180345","F31 HL167580","186993","R01 HL162304","R01 DK129350","R01 HG003988","R01 DE028599","T32 GM141742"],"pubmed_authors":["Visel A","Selleri L","Braasch I","Yun M","Smolikova J","Czarkwiani A","Mosimann C","Moran HR","Osterwalder M","Kemmler CL","Botschi S","Knapp D","Fitch OE","Lim F","Farley E","Hermosilla Aguayo V","Mannion BJ","Burger A","Rapp V","Kozmik Z"],"additional_accession":[]},"is_claimable":false,"name":"Conserved enhancer logic controls the notochord expression of vertebrate <i>Brachyury</i>.","description":"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 <i>Brachyury/T/TBXT</i> gene. Using transgenic assays in zebrafish, axolotl, and mouse, we discover three <i>Brachyury</i>-controlling notochord enhancers <i>T3</i>, <i>C</i>, and <i>I</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 <i>Brachyury</i>-driving notochord enhancers with the <i>brachyury/tbxtb</i> loci from diverse lineages of fishes dates their origin to the last common ancestor of jawed vertebrates. Our data define the enhancers for <i>Brachyury/T/TBXTB</i> notochord expression as ancient mechanism in axis development.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Apr","modification":"2025-04-19T04:38:59.672Z","creation":"2025-04-19T04:38:59.672Z"},"accession":"S-EPMC10153258","cross_references":{"pubmed":["37131681"],"doi":["10.1101/2023.04.20.536761"]}}