Dataset Information

Conserved enhancer logic controls the notochord expression of vertebrate Brachyury.

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.

SUBMITTER: Kemmler CL

PROVIDER: S-EPMC10153258 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Conserved enhancer logic controls the notochord expression of vertebrate Brachyury.

Kemmler Cassie L CL Smolikova Jana J Moran Hannah R HR Mannion Brandon J BJ Knapp Dunja D Lim Fabian F Czarkwiani Anna A Hermosilla Aguayo Viviana V Rapp Vincent V Fitch Olivia E OE Bötschi Seraina S Selleri Licia L Farley Emma E Braasch Ingo I Yun Maximina M Visel Axel A Osterwalder Marco M Mosimann Christian C Kozmik Zbynek Z Burger Alexa A

bioRxiv : the preprint server for biology 20230420

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-co ...[more]

PMID: 37131681

Similar Datasets

Project description:The vertebrate retina is patterned along its dorsal-ventral (DV) axis by signaling centers that provide each domain with distinct molecular and functional properties, including differential photoreceptor composition and opsin expression. Although the key DV patterning genes are well studied, the cisregulatory mechanisms that establish and maintain these territories remain poorly understood. To explore this regulatory landscape, we turned to the four-eyed fish Anableps anableps, whose large, protruding eyes and expanded ventral retina facilitate precise dissection of dorsal and ventral halves for spatially resolved genomics. Bulk RNA-seq of the Anableps dorsal and ventral retina regions recovered canonical DV markers, while bulk ATAC-seq revealed dorsally enriched ATAC-seq peaks residing within a low-genedensity region between efnb2a and gtpbp8. These putative cis-regulatory elements located to a 29 kb interval forming a contiguous enhancer cluster. Via Hi-C analysis, we identified a topologically associating domain (TAD) encompassing efnb2a, gtpbp8, and slc10a2, with a dorsal-enriched chromatin contact linking the enhancer cluster to the efnb2a promoter. Comparative genomics showed that this architecture is deeply conserved: the efnb2-slc10a2 synteny and TAD boundaries are maintained from human to zebrafish. To enable functional testing of this long regulatory interval, we strategically turned to Tetraodon nigroviridis, a species with one of the most compact vertebrate genomes, allowing nearly the entire orthologous enhancer cluster (~13 kb) to be cloned intact. Transgenic assays in both zebrafish and mouse demonstrated that this Tetraodon enhancer cluster drives dorsal retina-specific eGFP expression, underscoring the deep conservation of its regulatory function across vast phylogenetic distances. Together, these results highlight how a multi-species approach leveraging complementary strengths of model and non-model organisms can illuminate ancient regulatory mechanisms underlying vertebrate eye patterning.

Dataset Information

Conserved enhancer logic controls the notochord expression of vertebrate Brachyury.

Publications

Conserved enhancer logic controls the notochord expression of vertebrate <i>Brachyury</i>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets