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首页> 外文期刊>Molecular and Cellular Biology >CDP/Cux Stimulates Transcription from the DNA Polymerase α Gene Promoter
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CDP/Cux Stimulates Transcription from the DNA Polymerase α Gene Promoter

机译：CDP / Cux刺激DNA聚合酶α基因启动子的转录

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CDP/Cux (CCAAT-displacement protein/cut homeobox) contains four DNA binding domains, namely, three Cut repeats (CR1, CR2, and CR3) and a Cut homeodomain. CCAAT-displacement activity involves rapid but transient interaction with DNA. More stable DNA binding activity is up-regulated at the G1/S transition and was previously shown to involve an N-terminally truncated isoform, CDP/Cux p110, that is generated by proteolytic processing. CDP/Cux has been previously characterized as a transcriptional repressor. However, here we show that expression of reporter plasmids containing promoter sequences from the human DNA polymerase α (pol α), CAD, and cyclin A genes is stimulated in cotransfections with N-terminally truncated CDP/Cux proteins but not with full-length CDP/Cux. Moreover, expression of the endogenous DNA pol α gene was stimulated following the infection of cells with a retrovirus expressing a truncated CDP/Cux protein. Chromatin immunoprecipitation (ChIP) assays revealed that CDP/Cux was associated with the DNA pol α gene promoter specifically in the S phase. Using linker scanning analyses, in vitro DNA binding, and ChIP assays, we established a correlation between binding of CDP/Cux to the DNA pol α promoter and the stimulation of gene expression. Although we cannot exclude the possibility that stimulation of gene expression by CDP/Cux involved the repression of a repressor, our data support the notion that CDP/Cux participates in transcriptional activation. Notwithstanding its mechanism of action, these results establish CDP/Cux as an important transcriptional regulator in the S phase.
机译：CDP / Cux（CCAAT置换蛋白/剪切同源盒）包含四个DNA结合结构域，即三个剪切重复序列（CR1，CR2和CR3）和一个剪切同源域。 CCAAT置换活动涉及与DNA的快速但短暂的相互作用。更稳定的DNA结合活性在G 1 / S跃迁时被上调，先前已证明其涉及N端截短的亚型CDP / Cux p110，其是通过蛋白水解过程产生的。 CDP / Cux先前已被描述为转录阻遏物。但是，在这里我们显示，在与N末端截短的CDP / Cux蛋白共转染而不是全长CDP的共转染过程中，可刺激包含人类DNA聚合酶α（polα），CAD和cyclin A基因启动子序列的报告质粒的表达。 / Cux。此外，用表达截短的CDP / Cux蛋白的逆转录病毒感染细胞后，可刺激内源性DNA polα基因的表达。染色质免疫沉淀（ChIP）分析表明CDP / Cux与S阶段的DNA polα基因启动子特别相关。使用接头扫描分析，体外DNA结合和ChIP分析，我们建立了CDP / Cux与DNA polα启动子的结合与基因表达刺激之间的相关性。尽管我们不能排除CDP / Cux刺激基因表达涉及阻遏物抑制的可能性，但我们的数据支持CDP / Cux参与转录激活的观点。尽管有其作用机理，这些结果仍将CDP / Cux确立为S期的重要转录调节因子。

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