MicroRNAs play important roles in cell differentiation by acting as translational inhibitors of specific target genes. Here we show that human granulocytic differentiation is controlled by a regulatory circuitry involving miR-223 and two transcriptional factors, NFI-A and C/EBP?. The two factors compete for binding to the miR-223 promoter: NFI-A maintains miR-223 at low levels, whereas its replacement by C/EBP?, following retinoic acid (RA)-induced differentiation, upregulates miR-223 expression. The competition by C/EBP? and the granulocytic differentiation are favored by a negative-feedback loop in which miR-223 represses NFI-A translation. In line with this, both RNAi against NFI-A and ectopic expression of miR-223 in acute promyelocytic leukemia (APL) cells enhance differentiation, whereas miR-223 knockdown inhibits the differentiation response to RA. Altogether, our data indicate that miR-223 plays a crucial role during granulopoiesis and point to the NFI-A repression as an important molecular pathway mediating gene reprogramming in this cell lineage.

A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis / Fazi, Francesco; Rosa, Alessandro; Fatica, Alessandro; Gelmetti, V; DE MARCHIS, MARIA LAURA; Nervi, Clara; Bozzoni, Irene. - In: CELL. - ISSN 0092-8674. - STAMPA. - 123:(2005), pp. 819-831. [10.1016/j.cell.2005.09.023]

A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis.

FAZI, Francesco;ROSA, ALESSANDRO;FATICA, Alessandro;DE MARCHIS, MARIA LAURA;NERVI, Clara;BOZZONI, Irene
2005

Abstract

MicroRNAs play important roles in cell differentiation by acting as translational inhibitors of specific target genes. Here we show that human granulocytic differentiation is controlled by a regulatory circuitry involving miR-223 and two transcriptional factors, NFI-A and C/EBP?. The two factors compete for binding to the miR-223 promoter: NFI-A maintains miR-223 at low levels, whereas its replacement by C/EBP?, following retinoic acid (RA)-induced differentiation, upregulates miR-223 expression. The competition by C/EBP? and the granulocytic differentiation are favored by a negative-feedback loop in which miR-223 represses NFI-A translation. In line with this, both RNAi against NFI-A and ectopic expression of miR-223 in acute promyelocytic leukemia (APL) cells enhance differentiation, whereas miR-223 knockdown inhibits the differentiation response to RA. Altogether, our data indicate that miR-223 plays a crucial role during granulopoiesis and point to the NFI-A repression as an important molecular pathway mediating gene reprogramming in this cell lineage.
2005
01 Pubblicazione su rivista::01a Articolo in rivista
A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis / Fazi, Francesco; Rosa, Alessandro; Fatica, Alessandro; Gelmetti, V; DE MARCHIS, MARIA LAURA; Nervi, Clara; Bozzoni, Irene. - In: CELL. - ISSN 0092-8674. - STAMPA. - 123:(2005), pp. 819-831. [10.1016/j.cell.2005.09.023]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/363106
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