Sun Ying, Sun Qian, McNutt Michael A, Gong Yilei, Wang Jiaochen, Hou Lin, Shen Qi, Ling Yun, Chi Yingkai, Zhang Bo
Department of Pathology, Health Science Center of Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
Mol Cell Biochem. 2009 Jul;327(1-2):65-73. doi: 10.1007/s11010-009-0043-3. Epub 2009 Feb 13.
In a previous study, we demonstrated that telomerase transcriptional elements-interacting factor (TEIF) could up-regulate the expression of telomerase and DNA polymerase beta, increasing resistance to genotoxic agents. Here, we further report that TEIF can be stimulated by DNA damage and we have identified a cluster of repeated polypyrimidine tracts in the promoter of TEIF, which mediate both its basal transcription and its response to genotoxic agents. These polypyrimidine tracts are arranged in three types of repeating units and in each of these units there are 14 bp length tandem sequences, which are repeated three times. These sequences are also characteristically separated by an 11 bp interval sequence. Among these units, one type (5'-CCCCCCCATCCCCG-3') has been found to be involved in the transcriptional regulation of TEIF. At the same time, PTB1 (polypyrimidine tract-binding protein 1) has been shown to repress TEIF expression through interaction with this element. Up-regulation of TEIF may be achieved by PTB1 suppression that is induced by DNA damage, or by an olignucleotide decoy, which mediates reversal of suppression. This study provides new insight into the mechanism through which TEIF is involved in DNA damage response, together with insight into the role of polypyrimidine tracts in transcription regulation.
在先前的一项研究中，我们证明端粒酶转录元件相互作用因子（TEIF）可上调端粒酶和DNA聚合酶β的表达，增强对基因毒性剂的抗性。在此，我们进一步报道TEIF可被DNA损伤刺激，并且我们在TEIF启动子中鉴定出一组重复的多嘧啶序列，这些序列介导其基础转录及其对基因毒性剂的反应。这些多嘧啶序列以三种类型的重复单元排列，并且在每个单元中都有14bp长度的串联序列，重复三次。这些序列的特征还在于被11bp的间隔序列隔开。在这些单元中，已发现一种类型（5'-CCCCCCCATCCCCG-3'）参与TEIF的转录调控。同时，多嘧啶序列结合蛋白1（PTB1）已被证明通过与该元件相互作用来抑制TEIF表达。TEIF的上调可通过DNA损伤诱导的PTB1抑制或通过介导抑制逆转的寡核苷酸诱饵来实现。这项研究为TEIF参与DNA损伤反应的机制提供了新的见解，同时也为多嘧啶序列在转录调控中的作用提供了见解。
