The transcription factors Egr1 and Egr2 have opposing influences on adipocyte differentiation
The transcription factors Egr1 and Egr2 have opposing influences on adipocyte differentiation
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DOI：
10.1038/cdd.2009.11
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发表时间：
2009-05-01
影响因子：
12.4
通讯作者：
Siddle, K.
中科院分区：
文献类型：
--
作者：
Boyle, K. B.;Hadaschik, D.;Siddle, K.
含锌指转录因子Egr1(Krox24)和Egr2(Krox20)参与多种细胞的增殖和分化。早期的研究表明，Egr2在脂肪细胞分化中起积极作用，但Egr1在这方面的功能尚不清楚。我们比较了Egr1和Egr2在小鼠3T3-L1脂肪细胞分化中的作用。在加入分化鸡尾酒后，Egr1蛋白迅速被诱导，而Egr2蛋白最初保持在低水平，然后在第1天和第2天增加，伴随着Egr1的消失。与Egr2的作用相反，Egr1的异位表达抑制了分化，而Egr1的敲除则增强了分化。在分化培养基中去掉异丁基甲基黄嘌呤(IBMX)时，Egr1基因敲除的促成脂作用尤为显著。然而，Egr1基因敲除并不影响CCAAT/增强子结合蛋白(C/EBP)β蛋白的表达，也不影响CREB Ser133的磷酸化。此外，在荧光素酶报告实验中，Egr1不直接影响主要成脂转录因子C/EBPα或过氧化物酶体增殖物激活受体-γ2的启动子的活性。这些数据表明，Egr1和Egr2对脂肪细胞的分化起着相反的影响，为了维持适当的成脂水平，需要对两者进行仔细的调节。此外，IBMX的促分化作用包括抑制Egr1的抑制作用。
The zinc finger-containing transcription factors Egr1 (Krox24) and Egr2 (Krox20) have been implicated in the proliferation and differentiation of many cell types. Egr2 has earlier been shown to play a positive role in adipocyte differentiation, but the function of Egr1 in this context is unknown. We compared the roles of Egr1 and Egr2 in the differentiation of murine 3T3-L1 adipocytes. Egr1 protein was rapidly induced after addition of differentiation cocktail, whereas Egr2 protein initially remained low before increasing on days 1 and 2, concomitant with the disappearance of Egr1. In marked contrast to the effects of Egr2, differentiation was inhibited by ectopic expression of Egr1 and potentiated by knockdown of Egr1. The pro-adipogenic effects of Egr1 knockdown were particularly notable when isobutylmethylxanthine (IBMX) was omitted from the differentiation medium. However, knockdown of Egr1 did not affect CCAAT/enhancer binding protein (C/EBP) beta protein expression or phosphorylation of CREB Ser133. Further, Egr1 did not directly affect the activity of promoters for the master adipogenic transcription factors, C/EBP alpha or peroxisome proliferator-activated receptor-gamma 2, as assessed in luciferase reporter assays. These data indicate that Egr1 and Egr2 exert opposing influences on adipocyte differentiation and that the careful regulation of both is required for maintaining appropriate levels of adipogenesis. Further, the pro-differentiation effects of IBMX involve suppression of the inhibitory influence of Egr1.