Conserved enhancers control notochord expression of vertebrate Brachyury.

Autor:	Kemmler CL; Section of Developmental Biology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Smolikova J; Institute of Molecular Genetics of the ASCR, v. v. i., Prague, Czech Republic., Moran HR; Section of Developmental Biology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Mannion BJ; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.; Comparative Biochemistry Program, University of California, Berkeley, CA, 94720, USA., Knapp D; Technische Universität Dresden, CRTD Center for Regenerative Therapies Dresden, Dresden, Germany., Lim F; Department of Medicine, Health Sciences, University of California San Diego, La Jolla, CA, USA.; Department of Molecular Biology, Biological Sciences, University of California San Diego, La Jolla, CA, USA.; Biological Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA., Czarkwiani A; Technische Universität Dresden, CRTD Center for Regenerative Therapies Dresden, Dresden, Germany., Hermosilla Aguayo V; Program in Craniofacial Biology, University of California San Francisco, San Francisco, CA, USA.; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.; Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA, USA.; Department of Anatomy, University of California San Francisco, San Francisco, CA, USA., Rapp V; Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland., Fitch OE; Department of Integrative Biology and Ecology, Evolution and Behavior Program, Michigan State University, East Lansing, MI, USA., Bötschi S; Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland., Selleri L; Program in Craniofacial Biology, University of California San Francisco, San Francisco, CA, USA.; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.; Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA, USA.; Department of Anatomy, University of California San Francisco, San Francisco, CA, USA., Farley E; Department of Medicine, Health Sciences, University of California San Diego, La Jolla, CA, USA.; Department of Molecular Biology, Biological Sciences, University of California San Diego, La Jolla, CA, USA., Braasch I; Department of Integrative Biology and Ecology, Evolution and Behavior Program, Michigan State University, East Lansing, MI, USA., Yun M; Technische Universität Dresden, CRTD Center for Regenerative Therapies Dresden, Dresden, Germany.; Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany.; Cluster of Excellence Physics of Life, Technische Universität Dresden, Dresden, Germany., Visel A; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.; US Department of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.; School of Natural Sciences, University of California Merced, Merced, CA, USA., Osterwalder M; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.; Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.; Department of Cardiology, Bern University Hospital, Bern, Switzerland., Mosimann C; Section of Developmental Biology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Kozmik Z; Institute of Molecular Genetics of the ASCR, v. v. i., Prague, Czech Republic. zbynek.kozmik@img.cas.cz., Burger A; Section of Developmental Biology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. alexa.burger@cuanschutz.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2023 Oct 18; Vol. 14 (1), pp. 6594. Date of Electronic Publication: 2023 Oct 18.
DOI:	10.1038/s41467-023-42151-3
Abstrakt:	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. (© 2023. Springer Nature Limited.)
Databáze:	MEDLINE
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