Frank S R, Schroeder M, Fernandez P, Taubert S, Amati B
Department of Oncology, DNAX Research Institute, Palo Alto, California 94304, USA.
Genes Dev. 2001 Aug 15;15(16):2069-82. doi: 10.1101/gad.906601.
The Myc protein binds DNA and activates transcription by mechanisms that are still unclear. We used chromatin immunoprecipitation (ChIP) to evaluate Myc-dependent changes in histone acetylation at seven target loci. Upon serum stimulation of Rat1 fibroblasts, Myc associated with chromatin, histone H4 became locally hyperacetylated, and gene expression was induced. These responses were lost or severely impaired in Myc-deficient cells, but were restored by adenoviral delivery of Myc simultaneous with mitogenic stimulation. When targeted to chromatin in the absence of mitogens, Myc directly induced H4 acetylation. In addition, Myc recruited TRRAP to chromatin, consistent with a role for this cofactor in histone acetylation. Finally, unlike serum, Myc alone was very inefficient in inducing expression of most target genes. Myc therefore governs a step, most likely H4 acetylation, that is required but not sufficient for transcriptional activation. We propose that Myc acts as a permissive factor, allowing additional signals to activate target promoters.
Myc蛋白通过尚不清楚的机制与DNA结合并激活转录。我们利用染色质免疫沉淀法（ChIP）评估了七个靶位点上Myc依赖的组蛋白乙酰化变化。在血清刺激大鼠1成纤维细胞后，Myc与染色质结合，组蛋白H4局部高度乙酰化，基因表达被诱导。这些反应在Myc缺陷细胞中消失或严重受损，但通过腺病毒介导的Myc与促有丝分裂刺激同时递送得以恢复。当在无有丝分裂原的情况下靶向染色质时，Myc直接诱导H4乙酰化。此外，Myc将TRRAP募集到染色质上，这与该辅因子在组蛋白乙酰化中的作用一致。最后，与血清不同，单独的Myc在诱导大多数靶基因表达方面效率非常低。因此，Myc控制着一个步骤，很可能是H4乙酰化，这是转录激活所必需但不充分的条件。我们提出，Myc作为一个许可因子，允许其他信号激活靶启动子。
