Literature DB >> 18056638

The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation.

A Rosa1, M Ballarino, A Sorrentino, O Sthandier, F G De Angelis, M Marchioni, B Masella, A Guarini, A Fatica, C Peschle, I Bozzoni.   

Abstract

We describe a pathway by which the master transcription factor PU.1 regulates human monocyte/macrophage differentiation. This includes miR-424 and the transcriptional factor NFI-A. We show that PU.1 and these two components are interlinked in a finely tuned temporal and regulatory circuitry: PU.1 activates the transcription of miR-424, and this up-regulation is involved in stimulating monocyte differentiation through miR-424-dependent translational repression of NFI-A. In turn, the decrease in NFI-A levels is important for the activation of differentiation-specific genes such as M-CSFr. In line with these data, both RNAi against NFI-A and ectopic expression of miR-424 in precursor cells enhance monocytic differentiation, whereas the ectopic expression of NFI-A has an opposite effect. The interplay among these three components was demonstrated in myeloid cell lines as well as in human CD34+ differentiation. These data point to the important role of miR-424 and NFI-A in controlling the monocyte/macrophage differentiation program.

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Year:  2007        PMID: 18056638      PMCID: PMC2148386          DOI: 10.1073/pnas.0706963104

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


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