Wang Feng, Han Jinghua, Wang Li, Jing Ying, Zhu Zhu, Hui Dawei, Wang Zhaohui, Wang Yangzi, Dong Yang, Tan Tao
1 Faculty of Life Science and Technology, Kunming University of Science and Technology , Kunming, China .
2 Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology , Kunming, China .
Stem Cells Dev. 2017 May 15;26(10):743-750. doi: 10.1089/scd.2016.0309. Epub 2017 Mar 20.
It was previously reported that WD repeat domain 5 (Wdr5), a core member of the mammalian Trithorax complex, is a key regulator for the maintenance of embryonic stem (ES) cell pluripotency and somatic cell reprogramming. However, it remains unclear whether other factors are also involved in this process. Here, we show that CTCF is an upstream regulator of Wdr5: It physically associates with Wdr5 and further transcriptionally controls its expression by directly targeting the Wdr5 gene promoter. As a downstream effector, overexpression of Wdr5 can rescue ES cells from growth defects and decreased formation of induced pluripotent stem cells caused by CTCF knockdown. Our results reveal the functional relevance of CTCF and Wdr5, and they connect them to the re-establishment of pluripotency.
先前有报道称，WD重复结构域5（Wdr5）是哺乳动物三体胸复合物的核心成员，是维持胚胎干细胞（ES）多能性和体细胞重编程的关键调节因子。然而，尚不清楚是否有其他因素也参与这一过程。在此，我们表明CTCF是Wdr5的上游调节因子：它与Wdr5发生物理结合，并通过直接靶向Wdr5基因启动子进一步转录调控其表达。作为下游效应因子，Wdr5的过表达可以挽救因CTCF敲低而导致生长缺陷的ES细胞，并减少诱导多能干细胞的形成。我们的结果揭示了CTCF和Wdr5的功能相关性，并将它们与多能性的重新建立联系起来。
