The DNA replication factor MCM5 is essential for Stat1-mediated transcriptional activation
The DNA replication factor MCM5 is essential for Stat1-mediated transcriptional activation
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DOI：
10.1073/pnas.0507479102
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发表时间：
2005-10-11
影响因子：
11.1
通讯作者：
Zhang, JJ
中科院分区：
文献类型：
--
作者：
Snyder, M;He, W;Zhang, JJ
真核微染色体维持蛋白家族（MCM 2-MCM 7）是从酵母到人类进化上保守的。这些蛋白质是DNA复制所必需的。信号转导蛋白和转录激活蛋白对于导致基因表达调节的多种细胞因子和生长因子的信号转导至关重要。我们以前确定了Stat 1和MCM 5之间的强相互作用。然而，这种相互作用的生理意义尚不清楚。我们在这里显示的染色质免疫沉淀（ChIP）分析，MCM 5蛋白，以及其他成员的MCM家族，诱导招募Stat 1靶基因启动子响应细胞因子刺激。此外，显示MCM蛋白在转录延伸期间与RNA聚合酶11一起沿着移动。我们还确定了一个独立的结构域在MCM 5介导的Stat 1和MCM 5之间的相互作用，该结构域的过表达可以破坏Stat 1和MCM 5之间的相互作用，抑制Stat 1的转录活性。最后，我们使用RNA干扰技术表明，MCM 5是转录激活Stat 1靶基因所必需的。总之，这些结果表明，除了它们在DNA复制中的作用，MCM蛋白也是转录激活所必需的。
The eukaryotic minichromosome maintenance (MCM) family of proteins (MCM2-MCM7) is evolutionarily conserved from yeast to human. These proteins are essential for DNA replication. The signal transducer and activator of transcription proteins are critical for the signal transduction of a multitude of cytokines and growth factors leading to the regulation of gene expression. We previously identified a strong interaction between Stat1 and MCM5. However, the physiological significance of this interaction was not clear. We show here by chromatin immunoprecipitation (ChIP) analyses that the MCM5 protein, as well as other members of the MCM family, is inducibly recruited to Stat1 target gene promoters in response to cytokine stimulation. Furthermore, the MCM proteins are shown to move along with the RNA polymerase 11 during transcription elongation. We have also identified an independent domain in MCM5 that mediates the interaction between Stat1 and MCM5; overexpression of this domain can disrupt the interaction between Stat1 and MCM5 and inhibit Stat1 transcriptional activity. Finally, we used the RNA interference technique to show that MCM5 is essential for transcription activation of Stat1 target genes. Together, these results demonstrate that, in addition to their roles in DNA replication, the MCM proteins are also necessary for transcription activation.