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An ancestral Wnt-Brachyury feedback loop and vertebrate-specific recruitment of mesoderm-determining target genes revealed by comparative Brachyury target screens

ABSTRACT: Transcription factor brachyury plays a key role during mesoderm development in vertebrates. In this study we study study the effect of this transcription factor in diploblastic cnidarian model organism N. vectensis

ORGANISM(S): Nematostella vectensis

PROVIDER: GSE182573 | GEO | 2022/11/30

REPOSITORIES: GEO

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An ancestral Wnt-Brachyury feedback loop and vertebrate-specific recruitment of mesoderm-determining target genes revealed by comparative Brachyury target screens

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An ancestral Wnt-Brachyury feedback loop and vertebrate-specific recruitment of mesoderm-determining target genes revealed by comparative Brachyury target screens

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BRACHYURY directs histone acetylation to target loci during mesoderm development.

Project description:T-box transcription factors play essential roles in multiple aspects of vertebrate development. Here, we show that cooperative function of BRACHYURY (T) with histone-modifying enzymes is essential for mouse embryogenesis. A single point mutation (TY88A) results in decreased histone 3 lysine 27 acetylation (H3K27ac) at T target sites, including the T locus, suggesting that T autoregulates the maintenance of its expression and functions by recruiting permissive chromatin modifications to putative enhancers during mesoderm specification. Our data indicate that T mediates H3K27ac recruitment through a physical interaction with p300. In addition, we determine that T plays a prominent role in the specification of hematopoietic and endothelial cell types. Hematopoietic and endothelial gene expression programs are disrupted in TY88A mutant embryos, leading to a defect in the differentiation of hematopoietic progenitors. We show that this role of T is mediated, at least in part, through activation of a distal Lmo2 enhancer.

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The molecular basis of specific functions of Brachyury and Eomes for mesoderm and endoderm lineage specification

Project description:The Tbx factors Eomesodermin (Eomes) and Brachyury instruct endoderm and mesoderm specification. Both Tbx factors have common large overlap in chromatin binding sites, however their embryonic phenotypes of mutants largely differ. In this study, we delineate the distinct binding patterns and gene target sets of Eomes and Brachyury providing a molecular model of distinct fate specification programs.

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BRACHYURY orchestrates distinct mesoderm and endoderm gene regulatory networks in differentiating human embryonic stem cells

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