Unique N-terminal sequences in two Runx1 isoforms are dispensable for Runx1 function.
BMC Dev Biol
; 17(1): 14, 2017 10 18.
Article
en En
| MEDLINE
| ID: mdl-29047338
ABSTRACT
BACKGROUND:
The Runt-related transcription factors (Runx) are a family of evolutionarily conserved transcriptional regulators that play multiple roles in the developmental control of various cell types. Among the three mammalian Runx proteins, Runx1 is essential for definitive hematopoiesis and its dysfunction leads to human leukemogenesis. There are two promoters, distal (P1) and proximal (P2), in the Runx1 gene, which produce two Runx1 isoforms with distinct N-terminal amino acid sequences, P1-Runx1 and P2-Runx1. However, it remains unclear whether P2-Runx specific N-terminal sequence have any specific function for Runx1 protein.RESULTS:
To address the function of the P2-Runx1 isoform, we established novel mutant mouse models in which the translational initiation AUG (+1) codon for P2-Runx1 isoform was modulated. We found that a truncated P2-Runx1 isoform is translated from a downstream non-canonical AUG codon. Importantly, the truncated P2-Runx1 isoform is sufficient to support primary hematopoiesis, even in the absence of the P1-Runx1 isoform. Furthermore, the truncated P2-Runx1 isoform was able to restore defect in basophil development caused by loss of the P1-Runx1 isoform. The truncated P2-Runx1 isoform was more stable than the canonical P2-Runx1 isoform.CONCLUSIONS:
Our results demonstrate that the N-terminal sequences specific for P2-Runx1 are dispensable for Runx1 function, and likely serve as a de-stabilization module to regulate Runx1 production.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Subunidad alfa 2 del Factor de Unión al Sitio Principal
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
BMC Dev Biol
Asunto de la revista:
EMBRIOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Japón