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

被引:241
作者
Rosa, A. [1 ]
Ballarino, M. [1 ]
Sorrentino, A. [1 ,4 ]
Sthandier, O. [1 ]
De Angelis, F. G.
Marchioni, M.
Masella, B.
Guarini, A. [3 ]
Fatica, A. [1 ]
Peschle, C. [4 ]
Bozzoni, I. [1 ,2 ]
机构
[1] Univ Roma La Sapienza, Inst Pasteur Cenci Bolognetti, Dept Genet & Mol Biol, I-00185 Rome, Italy
[2] Univ Roma La Sapienza, Inst Mol Biol & Pathol, I-00185 Rome, Italy
[3] Univ Roma La Sapienza, Dept Cell Biotechnol & Hematol, I-00185 Rome, Italy
[4] Ist Super Sanita, Dept Hematol Oncol & Mol Med, I-00161 Rome, Italy
关键词
hematopoietic differentiation; microRNA; NFI-A; monocytopoiesis;
D O I
10.1073/pnas.0706963104
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:19849 / 19854
页数:6
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