Diverse logics and grammar encode notochord enhancers

Song, Benjamin P.; Ragsac, Michelle Franc; Tellez, Krissie; Jindal, Granton A.; Grudzien, Jessica L; Le, Sophia H; Farley, Emma K.

doi:10.1016/j.celrep.2023.112052

Cited by 13 publications

(16 citation statements)

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“…2 new; need to edit following Supplemental Figs.) or that hs_C responds to other upstream input than Brachyury/T/TBXTB (Song et al, 2023). Nevertheless, these data support the model in which Brachyury/T/TBXTB auto-regulates its own expression in the notochord through select regulatory elements (Beisaw et al, 2018;Schifferl et al, 2021).…”

Section: Dependence Of Human Brachyury Enhancers On T-box Motifsmentioning

confidence: 51%

“…Ciona experiments were performed at UCSD as described previously (Farley et al, 2015;Song et al, 2023). Adult Ciona intestinalis type A aka Ciona robusta (obtained from M-Rep) were maintained under constant illumination in seawater (obtained from Reliant Aquariums) at 18 °C.…”

Section: Ciona Reporter Assaysmentioning

confidence: 99%

“…Uncovering the cis-regulatory logic of vertebrate Brachyury notochord enhancer(s) will expand our understanding of the evolutionary history of this key developmental regulator and of the mechanisms leading to notochord formation. In particular, comparison to the Ciona Brachyury locus containing two upstream shadow enhancers with well-defined regulatory grammar (Farley et al, 2016;Song et al, 2023) may inform cis-regulatory adaptations at the onset of vertebrate emergence.…”

Section: Introductionmentioning

confidence: 99%

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Conserved enhancer logic controls the notochord expression of vertebrateBrachyury

Kemmler

Jana

Moran

et al. 2023

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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.

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Section: Dependence Of Human Brachyury Enhancers On T-box Motifsmentioning

confidence: 51%

Section: Ciona Reporter Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Conserved enhancer logic controls the notochord expression of vertebrateBrachyury

Kemmler

Jana

Moran

et al. 2023

Preprint

Self Cite

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“…When the FoxF enhancer with the affinity‐optimizing SNV drives expression of the gene FoxF there is ectopic expression of FoxF in anterior muscle cells, these cells migrate to the ventral midline and disrupt heart development; in the most severe case, Ciona juveniles develop with two hearts (shown in pink and orange). Images adapted from (Farley et al, 2015; Song et al, 2023).…”

Section: Figurementioning

confidence: 99%

“…We have found signatures of enhancer grammar conserved across chordates-in Ciona, mice, and humans (Song et al, 2023). We've also expanded to look at how violations in regulatory principles governing enhancers can drive organismal-level phenotypes in Ciona and other species, such as mice and humans (Jindal et al, 2023;Lim et al, 2022).…”

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confidence: 99%