主转录因子PU.1与miR-424之间的相互作用调节人类单核细胞/巨噬细胞的分化。
The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation.
作者信息
Rosa A, Ballarino M, Sorrentino A, Sthandier O, De Angelis F G, Marchioni M, Masella B, Guarini A, Fatica A, Peschle C, Bozzoni I
机构信息
Institute Pasteur Cenci-Bolognetti, Department of Genetics and Molecular Biology, Institute of Molecular Biology and Pathology, and Department of Cellular Biotechnologies and Hematology, University of Rome "La Sapienza", Rome, Italy.
出版信息
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19849-54. doi: 10.1073/pnas.0706963104. Epub 2007 Dec 3.
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.
我们描述了一种主要转录因子PU.1调节人类单核细胞/巨噬细胞分化的途径。这包括miR-424和转录因子NFI-A。我们表明，PU.1与这两个组分在一个精细调节的时间和调控回路中相互关联：PU.1激活miR-424的转录，并且这种上调通过miR-424依赖的NFI-A翻译抑制参与刺激单核细胞分化。反过来，NFI-A水平的降低对于诸如M-CSFr等分化特异性基因的激活很重要。与这些数据一致，针对NFI-A的RNA干扰以及前体细胞中miR-424的异位表达均增强单核细胞分化，而NFI-A的异位表达则具有相反的作用。这三个组分之间的相互作用在髓系细胞系以及人类CD34+分化中都得到了证实。这些数据表明miR-424和NFI-A在控制单核细胞/巨噬细胞分化程序中具有重要作用。
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