State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing, China.
Cancer Cell. 2012 Jan 17;21(1):92-104. doi: 10.1016/j.ccr.2011.12.016.
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.
肿瘤的发生是由于细胞周期失控和许多基因表达的改变。在这里，我们报告了一个基因 CREPT，它在多种人类肿瘤中优先表达。CREPT 的过表达加速了肿瘤的生长，而 CREPT 的缺失则显示出相反的效果。CREPT 通过与启动子结合来调节细胞周期蛋白 D1 的表达，增强其在体内和体外的转录，并与 RNA 聚合酶 II（RNAPII）相互作用。有趣的是，CREPT 促进染色质环的形成，并阻止 RNAPII 从基因的 3' 端终止位点读取。我们的研究结果揭示了一种机制，即 CREPT 通过增强 RNA 聚合酶 II 向启动子区域的募集，从而增加细胞周期蛋白 D1 的转录，可能还有染色质环的形成，从而促进肿瘤发生过程中的转录。
