Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETO oncoprotein.
Cancer Cell
; 12(5): 457-66, 2007 Nov.
Article
em En
| MEDLINE
| ID: mdl-17996649
ABSTRACT
Hematopoietic transcription factors are involved in chromosomal translocations, which generate fusion proteins contributing to leukemia pathogenesis. Analysis of patient's primary leukemia blasts revealed that those carrying the t(8;21) generating AML1/ETO, the most common acute myeloid leukemia-associated fusion protein, display low levels of a microRNA-223 (miR-223), a regulator of myelopoiesis. Here, we show that miR-223 is a direct transcriptional target of AML1/ETO. By recruiting chromatin remodeling enzymes at an AML1-binding site on the pre-miR-223 gene, AML1/ETO induces heterochromatic silencing of miR-223. Ectopic miR-223 expression, RNAi against AML1/ETO, or demethylating treatment enhances miR-223 levels and restores cell differentiation. Here, we identify an additional action for a leukemia fusion protein linking the epigenetic silencing of a microRNA locus to the differentiation block of leukemia.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
RNA Mensageiro
/
Leucemia
/
Regulação Leucêmica da Expressão Gênica
/
Proteínas Proto-Oncogênicas
/
Proteínas Oncogênicas
/
Inativação Gênica
/
MicroRNAs
/
Epigênese Genética
/
Proteínas de Ligação a DNA
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article