Zhang Hong-Mei, Li Li, Papadopoulou Nektaria, Hodgson Glenn, Evans Emma, Galbraith Matthew, Dear Mark, Vougier Stéphanie, Saxton Janice, Shaw Peter E
Centre for Biochemistry and Cell Biology, and School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
Nucleic Acids Res. 2008 May;36(8):2594-607. doi: 10.1093/nar/gkn099. Epub 2008 Mar 11.
Many eukaryotic genes are acutely regulated by extra-cellular signals. The c-fos serum response element (SRE) mediates transcriptional activation in response to mitogens through serum response factor (SRF)-dependent recruitment of Elk-1, a mitogen-activated protein kinase (MAPK)-responsive transcription factor. How subsequent events at SRE promoters stimulate initiation of transcription has yet to be fully resolved. Here we show that extra-cellular signal-regulated kinase (ERK) and mitogen and stress-activated kinase (MSK) are recruited to SRE promoter complexes in vitro and in vivo. Their recruitment in vitro correlates with Elk-1 binding and for ERK the D domain/KIM of Elk-1 is specifically involved. In vivo, recruitment of ERK and MSK is stimulated by mitogens, correlates with histone H3 phosphorylation and is impaired by Elk-1 knockdown. Immunocytochemistry and confocal microscopy reveal that ERK appears to associate to some extent with initiating rather than elongating RNA polymerase II. Taken together, our data add to the body of evidence implying that ERK and related MAPKs may fulfil a generic role at the promoters of acutely regulated genes.
许多真核基因受到细胞外信号的严格调控。c-fos血清反应元件（SRE）通过血清反应因子（SRF）依赖性招募Elk-1介导对有丝分裂原的转录激活，Elk-1是一种有丝分裂原激活蛋白激酶（MAPK）反应性转录因子。SRE启动子随后的事件如何刺激转录起始尚未完全解决。在这里，我们表明细胞外信号调节激酶（ERK）和有丝分裂原及应激激活激酶（MSK）在体外和体内被招募到SRE启动子复合物中。它们在体外的招募与Elk-1结合相关，对于ERK，Elk-1的D结构域/KIM特别参与其中。在体内，ERK和MSK的招募受到有丝分裂原的刺激，与组蛋白H3磷酸化相关，并且在Elk-1敲低时受损。免疫细胞化学和共聚焦显微镜显示，ERK似乎在一定程度上与起始而非延伸的RNA聚合酶II相关。总之，我们的数据增加了证据，表明ERK和相关的MAPK可能在急性调控基因的启动子上发挥普遍作用。
