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Publication : BRACHYURY directs histone acetylation to target loci during mesoderm development.

First Author  Beisaw A Year  2018
Journal  EMBO Rep Volume  19
Issue  1 Pages  118-134
PubMed ID  29141987 Mgi Jnum  J:257034
Mgi Id  MGI:6112862 Doi  10.15252/embr.201744201
Citation  Beisaw A, et al. (2018) BRACHYURY directs histone acetylation to target loci during mesoderm development. EMBO Rep 19(1):118-134
abstractText  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(Y88A)) 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 T(Y88A) 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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