JDP2, a repressor of AP-1, recruits a histone deacetylase 3 complex to inhibit the retinoic acid-induced differentiation of F9 cells
JDP2, a repressor of AP-1, recruits a histone deacetylase 3 complex to inhibit the retinoic acid-induced differentiation of F9 cells
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DOI：
10.1128/mcb.22.13.4815-4826.2002
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发表时间：
2002-07-01
影响因子：
5.3
通讯作者：
Yokoyama, KK
中科院分区：
文献类型：
--
作者：
Jin, CY;Li, HJ;Yokoyama, KK
c-jun基因的上调是维甲酸（RA）介导的胚胎癌F9细胞分化的关键事件。转录激活因子2（ATF-2）和p300在F9细胞分化过程中协同激活c-jun基因的转录。我们在这里表明，Jun二聚化蛋白2（JDP 2），AP-1的阻遏物的过表达，抑制c-jun基因的反式激活ATF-2和p300通过招募组蛋白脱乙酰酶3（HDAC 3）复合物，从而抑制RA诱导的c-jun基因的转录和抑制RA介导的F9细胞的分化。此外，染色质免疫沉淀试验表明，JDP 2/HDAC 3复合物，结合到未分化的F9细胞中的c-jun启动子内的分化反应元件，被取代的p300复合物响应RA，伴随着改变组蛋白乙酰化状态的染色质，启动转录的c-jun基因，和随后的分化的F9细胞。这些结果表明，JDP 2可能是控制F9细胞分化的关键因素，并为AP-1阻遏物发挥作用的机制提供了新的线索。
Up-regulation of the c-jun gene is a critical event in the retinoic acid (RA)-mediated differentiation of embryonal carcinoma F9 cells. Activating transcription factor 2 (ATF-2) and p300 cooperate in the activation of transcription of the c-jun gene during the differentiation of F9 cells. We show here that the overexpression of Jun dimerization protein 2 (JDP2), a repressor of AP-1, inhibits the transactivation of the c-jun gene by ATF-2 and p300 by recruitment of the histone deacetylase 3 (HDAC3) complex, thereby repressing the RA-induced transcription of the c-jun gene and inhibiting the RA-mediated differentiation of F9 cells. Moreover, chromatin immunoprecipitation assays showed that the JDP2/HDAC3 complex, which binds to the differentiation response element within the c-jun promoter in undifferentiated F9 cells, was replaced by the p300 complex in response to RA, with an accompanying change in the histone acetylation status of the chromatin, the initiation of transcription of the c-jun gene, and the subsequent differentiation of F9 cells. These results suggest that JDP2 may be a key factor that controls the commitment of F9 cells to differentiation and shed new light on the mechanism by which an AP-1 repressor functions.