CREPT Accelerates Tumorigenesis by Regulating the Transcription of Cell-Cycle-Related Genes
CREPT Accelerates Tumorigenesis by Regulating the Transcription of Cell-Cycle-Related Genes
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DOI：
10.1016/j.ccr.2011.12.016
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发表时间：
2012-01-17
期刊：
影响因子：
50.3
通讯作者：
Chang, Zhijie
中科院分区：
文献类型：
--
作者：
Lu, Dongdong;Wu, Yinyuan;Chang, Zhijie
肿瘤发生是由不受控制的细胞周期和许多基因表达的改变引起的。在这里，我们报告了一个基因CREPT，优先在不同的人类肿瘤中表达。CREPT的过表达加速肿瘤生长，而CREPT的耗竭则表现出相反的作用。CREPT通过与细胞周期蛋白D1的启动子结合，增强其在体内和体外的转录，并与RNA聚合酶II（RNAPII）相互作用来调节其表达。有趣的是，CREPT促进染色质环的形成，并阻止RNAPII通过基因的3'末端终止位点进行阅读。我们的研究结果揭示了一种机制，CREPT增加细胞周期蛋白D1的转录在肿瘤发生过程中，通过增强招募RNAPII的启动子区域，可能的话，以及染色质循环。
Tumorigenesis is caused by an uncontrolled cell cycle and the altered expression of many genes. Here, we report a gene CREPT that is preferentially expressed in diverse human tumors. Overexpression of CREPT accelerates tumor growth, whereas depletion of CREPT demonstrates a reversed effect. CREPT regulates cyclin D1 expression by binding to its promoter, enhancing its transcription both in vivo and in vitro, and interacting with RNA polymerase II (RNAPII). Interestingly, CREPT promotes the formation of a chromatin loop and prevents RNAPII from reading through the 3' end termination site of the gene. Our findings reveal a mechanism where CREPT increases cyclin D1 transcription during tumorigenesis, through enhancing the recruitment of RNAPII to the promoter region, possibly, as well as chromatin looping.