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


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.

SUBMITTER: Rosa A 

PROVIDER: S-EPMC2148386 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

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

Rosa A A   Ballarino M M   Sorrentino A A   Sthandier O O   De Angelis F G FG   Marchioni M M   Masella B B   Guarini A A   Fatica A A   Peschle C C   Bozzoni I I  

Proceedings of the National Academy of Sciences of the United States of America 20071203 50


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 N  ...[more]

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