A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis.
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/EBPalpha. The two factors compete for binding to the miR-223 promoter: NFI-A maintains miR-223 at low levels, whereas its replacement by C/EBPalpha, following retinoic acid (RA)-induced differentiation, upregulates miR-223 expression. The competition by C/EBPalpha 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.[1]References
- A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Fazi, F., Rosa, A., Fatica, A., Gelmetti, V., De Marchis, M.L., Nervi, C., Bozzoni, I. Cell (2005) [Pubmed]
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