Details

Autor(en) / Beteiligte

• Fazi, Francesco
• Racanicchi, Serena
• Zardo, Giuseppe
• Starnes, Linda M.
• Mancini, Marco
• Travaglini, Lorena
• Diverio, Daniela
• Ammatuna, Emanuele
• Cimino, Giuseppe
• Lo-Coco, Francesco
• Grignani, Francesco
• Nervi, Clara

Titel

Epigenetic Silencing of the Myelopoiesis Regulator microRNA-223 by the AML1/ETO Oncoprotein

Ist Teil von

• Cancer cell, 2007-11, Vol.12 (5), p.457-466

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.