Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence.
EMBO J
; 34(6): 759-77, 2015 Mar 12.
Article
en En
| MEDLINE
| ID: mdl-25564442
ABSTRACT
Scl/Tal1 confers hemogenic competence and prevents ectopic cardiomyogenesis in embryonic endothelium by unknown mechanisms. We discovered that Scl binds to hematopoietic and cardiac enhancers that become epigenetically primed in multipotent cardiovascular mesoderm, to regulate the divergence of hematopoietic and cardiac lineages. Scl does not act as a pioneer factor but rather exploits a pre-established epigenetic landscape. As the blood lineage emerges, Scl binding and active epigenetic modifications are sustained in hematopoietic enhancers, whereas cardiac enhancers are decommissioned by removal of active epigenetic marks. Our data suggest that, rather than recruiting corepressors to enhancers, Scl prevents ectopic cardiogenesis by occupying enhancers that cardiac factors, such as Gata4 and Hand1, use for gene activation. Although hematopoietic Gata factors bind with Scl to both activated and repressed genes, they are dispensable for cardiac repression, but necessary for activating genes that enable hematopoietic stem/progenitor cell development. These results suggest that a unique subset of enhancers in lineage-specific genes that are accessible for regulators of opposing fates during the time of the fate decision provide a platform where the divergence of mutually exclusive fates is orchestrated.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Madre Hematopoyéticas
/
Diferenciación Celular
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Proteínas Proto-Oncogénicas
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Elementos de Facilitación Genéticos
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Regulación del Desarrollo de la Expresión Génica
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Mioblastos Cardíacos
/
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
/
Mesodermo
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
EMBO J
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos