Regulation of cyclin D2 gene expression by the Myc/Max/Mad network:: Myc-dependent TRRAP recruitment and histone acetylation at the cyclin D2 promoter
Regulation of cyclin D2 gene expression by the Myc/Max/Mad network:: Myc-dependent TRRAP recruitment and histone acetylation at the cyclin D2 promoter
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DOI：
10.1101/gad.907901
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发表时间：
2001-08-15
影响因子：
10.5
通讯作者：
Lüscher, B
中科院分区：
文献类型：
--
作者：
Bouchard, C;Dittrich, O;Lüscher, B
Myc癌蛋白部分通过细胞周期蛋白D2基因的转录上调来促进细胞周期进程。我们现在表明，Myc是结合到细胞周期蛋白D2启动子在体内。Myc的结合以MycBoxII/TRRAP依赖的方式诱导单个核小体的细胞周期蛋白D2表达和组蛋白乙酰化。在分化的HL 60细胞中，细胞周期蛋白D2 mRNA表达下调之前，启动子占据从Myc/Max转换为Mad/Max复合物，TRRAP结合丧失，HDAC 1结合增加和组蛋白脱乙酰化。因此，TRRAP的募集和组蛋白乙酰化的调节对于Myc的转录激活至关重要。
Myc oncoproteins promote cell cycle progression in part through the transcriptional up-regulation of the cyclin D2 gene. We now show that Myc is bound to the cyclin D2 promoter in vivo. Binding of Myc induces cyclin D2 expression and histone acetylation at a single nucleosome in a MycBoxII/TRRAP-dependent manner. Downregulation of cyclin D2 mRNA expression in differentiating HL60 cells is preceded by a switch of promoter occupancy from Myc/Max to Mad/Max complexes, loss of TRRAP binding, increased HDAC1 binding, and histone deacetylation. Thus, recruitment of TRRAP and regulation of histone acetylation are critical for transcriptional activation by Myc.