The CpG Dinucleotide Adjacent to a κB Site Affects NF-κB Function through Its Methylation

نویسندگان

  • Tao Wang
  • Jinge Li
  • Ke Ding
  • Li Zhang
  • Qiuru Che
  • Xiuming Sun
  • Yumeng Dai
  • Wei Sun
  • Meiying Bao
  • Xiaochun Wang
  • Liquan Yang
  • Zhiwei Li
چکیده

NF-κB is an important transcription factor that plays critical roles in cell survival, proliferation, inflammation, and cancers. Although the majority of experimentally identified functional NF-κB binding sites (κB sites) match the consensus sequence, there are plenty of non-functional NF-κB consensus sequences in the genome. We analyzed the surrounding sequences of the known κB sites that perfectly match the GGGRNNYYCC consensus sequence and identified the nucleotide at the -1 position of κB sites as a key contributor to the binding of the κB sites by NF-κB. We demonstrated that a cytosine at the -1 position of a κB site (-1C) could be methylated, which thereafter impaired NF-κB binding and/or function. In addition, all -1C κB sites are located in CpG islands and are conserved during evolution only when they are within CpG islands. Interestingly, when there are multiple NF-κB binding possibilities, methylation of -1C might increase NF-κB binding. Our finding suggests that a single nucleotide at the -1 position of a κB site could be a critical factor in NF-κB functioning and could be exploited as an additional manner to regulate the expression of NF-κB target genes.

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عنوان ژورنال:

دوره 18  شماره 

صفحات  -

تاریخ انتشار 2017