1. SNIP1 Recruits TET2 to Regulate c-MYC Target Genes and Cellular DNA Damage Response
- Author
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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, and Guan, Kun-Liang
- Subjects
Biochemistry and Cell Biology ,Genetics ,Biological Sciences ,Human Genome ,Cancer ,1.1 Normal biological development and functioning ,Underpinning research ,Generic health relevance ,Animals ,Apoptosis ,Biocatalysis ,Cell Line ,Tumor ,Cisplatin ,DNA Breaks ,Double-Stranded ,DNA Damage ,DNA-Binding Proteins ,Dioxygenases ,Gene Expression Regulation ,HEK293 Cells ,Humans ,Intracellular Signaling Peptides and Proteins ,Mice ,Inbred BALB C ,Mice ,Nude ,Protein Binding ,Proto-Oncogene Proteins ,Proto-Oncogene Proteins c-myc ,RNA-Binding Proteins ,Transcription ,Genetic ,DNA damage ,DNA demethylation ,SNIP1 ,TET2 ,c-MYC ,cell death ,transcription ,Medical Physiology ,Biological sciences - 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.
- Published
- 2018