Bouchard C, Dittrich O, Kiermaier A, Dohmann K, Menkel A, Eilers M, Lüscher B
Institute for Molecular Biology and Tumor Research, 35033 Marburg, Germany.
Genes Dev. 2001 Aug 15;15(16):2042-7. doi: 10.1101/gad.907901.
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. Down-regulation 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.
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在体内与细胞周期蛋白D2启动子结合。Myc的结合以MycBoxII/TRRAP依赖的方式诱导细胞周期蛋白D2表达和单个核小体处的组蛋白乙酰化。在分化的HL60细胞中，细胞周期蛋白D2 mRNA表达下调之前，启动子占据情况从Myc/Max复合物转变为Mad/Max复合物，TRRAP结合丧失，HDAC1结合增加以及组蛋白去乙酰化。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。
