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

Francesco Fazi, Alessandro Rosa, Alessandro Fatica, Vania Gelmetti, Maria Laura De Marchis, Clara Nervi, Irene Bozzoni

Research output: Contribution to journalArticlepeer-review

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/EBPα. The two factors compete for binding to the miR-223 promoter: NFI-A maintains miR-223 at low levels, whereas its replacement by C/EBPα, following retinoic acid (RA)-induced differentiation, upregulates miR-223 expression. The competition by C/EBPα 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.

Original languageEnglish
Pages (from-to)819-831
Number of pages13
JournalCell
Volume123
Issue number5
DOIs
Publication statusPublished - Dec 2 2005

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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