The erythroid phenotype of EKLF-null mice: defects in hemoglobin metabolism and membrane stability.
Mol Cell Biol
; 25(12): 5205-14, 2005 Jun.
Article
em En
| MEDLINE
| ID: mdl-15923635
ABSTRACT
Development of red blood cells requires the correct regulation of cellular processes including changes in cell morphology, globin expression and heme synthesis. Transcription factors such as erythroid Kruppel-like factor EKLF (Klf1) play a critical role in erythropoiesis. Mice lacking EKLF die around embryonic day 14 because of defective definitive erythropoiesis, partly caused by a deficit in beta-globin expression. To identify additional target genes, we analyzed the phenotype and gene expression profiles of wild-type and EKLF null primary erythroid progenitors that were differentiated synchronously in vitro. We show that EKLF is dispensable for expansion of erythroid progenitors, but required for the last steps of erythroid differentiation. We identify EKLF-dependent genes involved in hemoglobin metabolism and membrane stability. Strikingly, expression of these genes is also EKLF-dependent in primitive, yolk sac-derived, blood cells. Consistent with lack of upregulation of these genes we find previously undetected morphological abnormalities in EKLF-null primitive cells. Our data provide an explanation for the hitherto unexplained severity of the EKLF null phenotype in erythropoiesis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
/
Fatores de Transcrição
/
Hemoglobinas
/
Membrana Celular
/
Regulação da Expressão Gênica
/
Proteínas de Ligação a DNA
/
Eritrócitos
/
Eritropoese
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article