Zippo Alessio, Serafini Riccardo, Rocchigiani Marina, Pennacchini Susanna, Krepelova Anna, Oliviero Salvatore
Dipartimento di Biologia Molecolare Università di Siena, Siena, Italy.
Cell. 2009 Sep 18;138(6):1122-36. doi: 10.1016/j.cell.2009.07.031.
The phosphorylation of the serine 10 at histone H3 has been shown to be important for transcriptional activation. Here, we report the molecular mechanism through which H3S10ph triggers transcript elongation of the FOSL1 gene. Serum stimulation induces the PIM1 kinase to phosphorylate the preacetylated histone H3 at the FOSL1 enhancer. The adaptor protein 14-3-3 binds the phosphorylated nucleosome and recruits the histone acetyltransferase MOF, which triggers the acetylation of histone H4 at lysine 16 (H4K16ac). This histone crosstalk generates the nucleosomal recognition code composed of H3K9acS10ph/H4K16ac determining a nucleosome platform for the bromodomain protein BRD4 binding. The recruitment of the positive transcription elongation factor b (P-TEFb) via BRD4 induces the release of the promoter-proximal paused RNA polymerase II and the increase of its processivity. Thus, the single phosphorylation H3S10ph at the FOSL1 enhancer triggers a cascade of events which activate transcriptional elongation.
组蛋白H3丝氨酸10位点的磷酸化已被证明对转录激活很重要。在此，我们报告了H3S10ph触发FOSL1基因转录延伸的分子机制。血清刺激诱导PIM1激酶使FOSL1增强子处的预乙酰化组蛋白H3磷酸化。衔接蛋白14-3-3结合磷酸化的核小体并募集组蛋白乙酰转移酶MOF，后者触发组蛋白H4赖氨酸16位点的乙酰化（H4K16ac）。这种组蛋白串扰产生了由H3K9acS10ph/H4K16ac组成的核小体识别密码，为溴结构域蛋白BRD4结合确定了一个核小体平台。通过BRD4募集正性转录延伸因子b（P-TEFb）可诱导启动子近端暂停的RNA聚合酶II释放并增加其持续合成能力。因此，FOSL1增强子处的单个磷酸化H3S10ph触发了一系列激活转录延伸的事件。
