| 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. |