c-Myb and p300 regulate hematopoietic stem cell proliferation and differentiation.
Dev Cell
; 8(2): 153-66, 2005 Feb.
Article
em En
| MEDLINE
| ID: mdl-15691758
ABSTRACT
Precise control of hematopoietic stem cell (HSC) proliferation and differentiation is needed to maintain a lifetime supply of blood cells. Using genome-wide ENU mutagenesis and phenotypic screening, we have identified a mouse line that harbors a point mutation in the transactivation (TA) domain of the transcription factor c-Myb (M303V), which reduces c-Myb-dependent TA by disrupting its interaction with the transcriptional coactivator p300. The biological consequences of the c-Myb(M303V/M303V) mutation include thrombocytosis, megakaryocytosis, anemia, lymphopenia, and the absence of eosinophils. Detailed analysis of hematopoiesis in c-Myb(M303V/M303V) mice reveals distinct blocks in T cell, B cell, and red blood cell development, as well as a remarkable 10-fold increase in the number of HSCs. Cell cycle analyses show that twice as many HSCs from c-Myb(M303V/M303V) animals are actively cycling. Thus c-Myb, through interaction with p300, controls the proliferation and differentiation of hematopoietic stem and progenitor cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Proteínas Nucleares
/
Transativadores
/
Proteínas Proto-Oncogênicas c-myb
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Dev Cell
Assunto da revista:
EMBRIOLOGIA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos