The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation
The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation
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DOI：
10.1073/pnas.0706963104
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发表时间：
2007-12-11
影响因子：
11.1
通讯作者：
Bozzoni, I.
中科院分区：
文献类型：
--
作者：
Rosa, A.;Ballarino, M.;Bozzoni, I.
我们描述了主转录因子PU.1调控人类单核细胞/巨噬细胞分化的途径。这包括miR-424和转录因子NFI-A。我们发现PU.1和这两个成分在一个精细调节的时间和调节回路中相互关联：PU.1激活miR-424的转录，这种上调通过miR-424依赖的NFI-A的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M-CSFr等分化特异性基因的激活是重要的。根据这些数据，针对NFI-A的RNAi和前体细胞中miR-424的异位表达都能增强单核细胞分化，而NFI-A的异位表达则具有相反的作用。这三种成分之间的相互作用在骨髓细胞系和人类CD34+分化中得到证实。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的重要作用。
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.