SNIP1 Recruits TET2 to Regulate c-MYC Target Genes and Cellular DNA Damage Response.

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.
Mesh Terms:
Animals, Apoptosis, Biocatalysis, Cell Line, Tumor, Cisplatin, DNA Breaks, Double-Stranded, DNA Damage, DNA-Binding Proteins, 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, Transcription, Genetic
Cell Rep
Date: Dec. 06, 2017
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