BRACHYURY directs histone acetylation to target loci during mesoderm development.
EMBO Rep
; 19(1): 118-134, 2018 01.
Article
em En
| MEDLINE
| ID: mdl-29141987
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Histonas
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Proteínas com Domínio T
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Desenvolvimento Embrionário
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Fatores de Transcrição de p300-CBP
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Proteínas Fetais
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Células-Tronco Embrionárias Murinas
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Mesoderma
Limite:
Animals
Idioma:
En
Revista:
EMBO Rep
Ano de publicação:
2018
Tipo de documento:
Article