CTCF Mediates Replicative Senescence Through POLD1.
CTCF Mediates Replicative Senescence Through POLD1.
复制标题
CTCF 通过 POLD1 介导复制衰老
DOI：
10.3389/fcell.2021.618586
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发表时间：
2021
影响因子：
5.5
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Hou Y;Song Q;Gao S;Zhang X;Wang Y;Liu J;Fu J;Cao M;Wang P
POLD 1是DNA聚合酶δ的催化亚基，在DNA合成和DNA修复过程中起关键作用。此外，POLD 1在复制性衰老中下调以介导衰老。在任何情况下，POLD 1表达的年龄相关下调的组件尚未得到充分解释。本文从转录水平阐明了POLD 1的调控机制，发现转录因子CCCTC结合因子（CTCF）与POLD 1启动子区有两个位点结合。CTCF对POLD 1启动子的结合水平似乎与衰老有关，并被证实受CTCF水平的正控制。此外，在转染短发夹状RNA（shRNA）-CTCF、pLenti-CMV-CTCF、shRNA-POLD 1和pLenti-CMV-POLD 1的细胞中检测到细胞衰老特征，结果表明CTCF可能与POLD 1在衰老中的表达改变有关。总之，CTCF的POLD 1启动子的结合水平干预了与年龄相关的CTCF减少，并在衰老过程中下调POLD 1的表达。此外，CTCF介导的POLD 1转录的减少加速了细胞衰老的进程。
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.
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