Hou Yuli, Song Qiao, Gao Shichao, Zhang Xiaomin, Wang Yaqi, Liu Jing, Fu Jingxuan, Cao Min, Wang Peichang
Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing, China.
Front Cell Dev Biol. 2021 Feb 22;9:618586. doi: 10.3389/fcell.2021.618586. eCollection 2021.
POLD1, the catalytic subunit of DNA polymerase δ, plays a critical role in DNA synthesis and DNA repair processes. Moreover, POLD1 is downregulated in replicative senescence to mediate aging. In any case, the components of age-related downregulation of POLD1 expression have not been fully explained. In this article, we elucidate the mechanism of the regulation of POLD1 at the transcription level and found that the transcription factor CCCTC-binding factor (CTCF) was bound to the POLD1 promoter area in two sites. The binding level of CTCF for the POLD1 promoter appeared to be related to aging and was confirmed to be positively controlled by the CTCF level. Additionally, cell senescence characteristics were detected within the cells transfected with short hairpin RNA (shRNA)-CTCF, pLenti-CMV-CTCF, shRNA-POLD1, and pLenti-CMV-POLD1, and the results showed that the CTCF may contribute to the altered expression of POLD1 in aging. In conclusion, the binding level of CTCF for the POLD1 promoter intervened by an age-related decrease in CTCF and downregulated the POLD1 expression in aging. Moreover, the decrease in CTCF-mediated POLD1 transcription accelerates the progression of cell aging.
DNA聚合酶δ的催化亚基POLD1在DNA合成和DNA修复过程中发挥关键作用。此外，POLD1在复制性衰老过程中表达下调以介导衰老。无论如何，POLD1表达与年龄相关下调的组成部分尚未得到充分解释。在本文中，我们阐明了POLD1在转录水平的调控机制，发现转录因子CCCTC结合因子（CTCF）在两个位点与POLD1启动子区域结合。CTCF对POLD1启动子的结合水平似乎与衰老有关，并被证实受CTCF水平的正向调控。此外，在用短发夹RNA（shRNA）-CTCF、pLenti-CMV-CTCF、shRNA-POLD1和pLenti-CMV-POLD1转染的细胞中检测到细胞衰老特征，结果表明CTCF可能导致衰老过程中POLD1表达的改变。总之，CTCF对POLD1启动子的结合水平受与年龄相关的CTCF减少的干预，导致衰老过程中POLD1表达下调。此外，CTCF介导的POLD1转录减少加速了细胞衰老的进程。
