Complexity in transcription control at the activation domain-mediator interface.
Complexity in transcription control at the activation domain-mediator interface.
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DOI：
10.1126/scisignal.1164302
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发表时间：
2009-05-05
影响因子：
7.3
通讯作者：
Berk AJ
中科院分区：
文献类型：
--
作者：
Balamotis MA;Pennella MA;Stevens JL;Wasylyk B;Belmont AS;Berk AJ
转录延长由聚合酶II暂停在Egr 1启动子激活的丝裂原活化蛋白激酶磷酸化的三元复合因子（TCF）ELK 1结合在多个上游位点和随后的磷酸化ELK 1通过MED23亚基与介体相互作用。因此，Med23敲除（KO）几乎消除了胚胎干（ES）细胞中的Egr 1（早期生长反应因子1）转录，在启动子处留下暂停的聚合酶。然而，Med23 KO没有消除成纤维细胞中的Egr 1转录。染色质免疫沉淀分析和荧光标记的TCF衍生物和介质亚基的直接可视化显示，三个密切相关的TCF绑定到相同的控制区域。这些TCFs的相对量对MED23的损失有不同的反应，在ES细胞和成纤维细胞中不同。转录组分析表明，在两种细胞类型中表达的大多数基因，如Egr 1，受到两种细胞类型中对相同信号转导途径反应不同的替代转录因子的调节。
Transcript elongation by polymerase II paused at the Egr1 promoter is activated by mitogen-activated protein kinase phosphorylation of the ternary complex factor (TCF) ELK1 bound at multiple upstream sites and subsequent phospho-ELK1 interaction with mediator through the MED23 subunit. Consequently, Med23 knockout (KO) nearly eliminates Egr1 (early growth response factor 1) transcription in embryonic stem (ES) cells, leaving a paused polymerase at the promoter. Med23 KO did not, however, eliminate Egr1 transcription in fibroblasts. Chromatin immunoprecipitation analysis and direct visualization of fluorescently labeled TCF derivatives and mediator subunits revealed that three closely related TCFs bound to the same control regions. The relative amounts of these TCFs, which responded differently to the loss of MED23, differed in ES cells and fibroblasts. Transcriptome analysis suggests that most genes expressed in both cell types, such as Egr1, are regulated by alternative transcription factors in the two cell types that respond differently to the same signal transduction pathways.