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BRACHYURY directs histone acetylation to target loci during mesoderm development.


ABSTRACT: 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.

SUBMITTER: Beisaw A 

PROVIDER: S-EPMC5757217 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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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 (T<sup>Y88A</sup>) results in decreased histone 3 lysine 27 acetylation (H3K27ac) at T target sites, including the <i>T</i> locus, suggesting that T autoregulates the maintenance of its expression and functions by recruiting permissive chromatin modifica  ...[more]

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