학술논문
SNIP1 Recruits TET2 to Regulate c-MYC Target Genes and Cellular DNA Damage Response
Document Type
article
Author
Chen, Lei-Lei; Lin, Huai-Peng; Zhou, Wen-Jie; He, Chen-Xi; Zhang, Zhi-Yong; Cheng, Zhou-Li; Song, Jun-Bin; Liu, Peng; Chen, Xin-Yu; Xia, Yu-Kun; Chen, Xiu-Fei; Sun, Ren-Qiang; Zhang, Jing-Ye; Sun, Yi-Ping; Song, Lei; Liu, Bing-Jie; Du, Rui-Kai; Ding, Chen; Lan, Fei; Huang, Sheng-Lin; Zhou, Feng; Liu, Suling; Xiong, Yue; Ye, Dan; Guan, Kun-Liang
Source
Cell Reports. 25(6)
Subject
Language
Abstract
The TET2 DNA dioxygenase regulates gene expression by catalyzing demethylation of 5-methylcytosine, thus epigenetically modulating the genome. TET2 does not contain a sequence-specific DNA-binding domain, and how it is recruited to specific genomic sites is not fully understood. Here we carried out a mammalian two-hybrid screen and identified multiple transcriptional regulators potentially interacting with TET2. The SMAD nuclear interacting protein 1 (SNIP1) physically interacts with TET2 and bridges TET2 to bind several transcription factors, including c-MYC. SNIP1 recruits TET2 to the promoters of c-MYC target genes, including those involved in DNA damage response and cell viability. TET2 protects cells from DNA damage-induced apoptosis dependending on SNIP1. Our observations uncover a mechanism for targeting TET2 to specific promoters through a ternary interaction with a co-activator and many sequence-specific DNA-binding factors. This study also reveals a TET2-SNIP1-c-MYC pathway in mediating DNA damage response, thereby connecting epigenetic control to maintenance of genome stability.