Cbfß2 controls differentiation of and confers homing capacity to prethymic progenitors.
J Exp Med
; 215(2): 595-610, 2018 02 05.
Article
en En
| MEDLINE
| ID: mdl-29343500
ABSTRACT
Multipotent hematopoietic progenitors must acquire thymus-homing capacity to initiate T lymphocyte development. Despite its importance, the transcriptional program underlying this process remains elusive. Cbfß forms transcription factor complexes with Runx proteins, and here we show that Cbfß2, encoded by an RNA splice variant of the Cbfb gene, is essential for extrathymic differentiation of T cell progenitors. Furthermore, Cbfß2 endows extrathymic progenitors with thymus-homing capacity by inducing expression of the principal thymus-homing receptor, Ccr9. This occurs via direct binding of Cbfß2 to cell type-specific enhancers, as is observed in Rorγt induction during differentiation of lymphoid tissue inducer cells by activation of an intronic enhancer. As in mice, an alternative splicing event in zebrafish generates a Cbfß2-specific mRNA, important for ccr9 expression. Thus, despite phylogenetically and ontogenetically variable sites of origin of T cell progenitors, their robust thymus-homing capacity is ensured by an evolutionarily conserved mechanism emerging from functional diversification of Runx transcription factor complexes by acquisition of a novel splice variant.
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Banco de datos:
MEDLINE
Asunto principal:
Proteínas de Pez Cebra
/
Subunidad beta del Factor de Unión al Sitio Principal
/
Células Precursoras de Linfocitos T
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón