Interferon regulatory factor-2 drives megakaryocytic differentiation
Interferon regulatory factor-2 drives megakaryocytic differentiation
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DOI：
10.1042/bj20031166
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发表时间：
2004-01-15
影响因子：
4.1
通讯作者：
Battistini, A
中科院分区：
文献类型：
--
作者：
Stellacci, E;Testa, U;Battistini, A
IRFs [IFN（干扰素）调节因子]构成了一个转录因子家族，参与IFN信号传导和免疫系统的发育和分化。IRF-2通常被描述为IRF-1介导的IFN和IFN诱导基因转录的拮抗剂;然而，最近已鉴定为一些基因的转录激活剂，例如编码历史H4、VCAM-1（血管细胞粘附分子-1）和Fas配体的基因。在生物学上，IRF-2在细胞生长调节中起重要作用，并且已被证明是潜在的癌基因。在基因敲除小鼠中的研究也表明IRF-2与造血细胞的分化和功能有关。在这里，我们表明，IRF-2在骨髓祖细胞系的表达导致这些细胞向巨核细胞谱系的重编程，使他们能够响应血小板生成素，细胞形态和特异性分化标志物的表达进行评估。还证实了参与巨核细胞谱系发育的转录因子如加塔-1、加塔-2、FOG-1（加塔-1的朋友）和NF-E2（核因子-红细胞-2）的上调，以及血小板生成素受体的转录刺激。我们的研究结果为IRF-2在巨核细胞分化诱导中的关键作用提供了证据，并揭示了该转录因子在调节细胞反应中的显著功能多样性。
IRFs [IFN (interferon) regulatory factors] constitute a family of transcription factors involved in IFN signalling and in the development and differentiation of the immune system. IRF-2 has generally been described as an antagonist of IRF-1-mediated transcription of IFN and IFN-inducible genes; however, it has been recently identified as a transcriptional activator of some genes, such as those encoding historic H4, VCAM-1 (vascular cell adhesion molecule-1) and Fas ligand. Biologically, IRF-2 plays an important role in cell growth regulation and has been shown to be a potential oncogene. Studies in knock-out mice have also implicated IRF-2 in the differentiation and functionality of haematopoietic cells. Here we show that IRF-2 expression in a myeloid progenitor cell line leads to reprogramming of these cells towards the megakaryocytic lineage and enables them to respond to thrombopoietin, as assessed by cell morphology and expression of specific differentiation markers. Up-regulation of transcription factors involved in the development of the megakaryocytic lineage, such as GATA-1, GATA-2, FOG-1 (friend of GATA-1) and NF-E2 (nuclear factor-erythroid-2), and transcriptional stimulation of the thrombopoietin receptor were also demonstrated. Our results provide evidence for a key role for IRF-2 in the induction of a programme of megakaryocytic differentiation, and reveal a remarkable functional diversity of this transcription factor in the regulation of cellular responses.