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Int. J. Mol. Sci. 2017, 18(3), 528;

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

The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Science, Jilin University, Changchun 130012, China
Author to whom correspondence should be addressed.
Academic Editor: Charles J. Malemud
Received: 26 December 2016 / Revised: 18 February 2017 / Accepted: 21 February 2017 / Published: 1 March 2017
(This article belongs to the Section Biochemistry)
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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. View Full-Text
Keywords: NF-κB; consensus sequence; CpG islands; methylation NF-κB; consensus sequence; CpG islands; methylation

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Wang, T.; Li, J.; Ding, K.; Zhang, L.; Che, Q.; Sun, X.; Dai, Y.; Sun, W.; Bao, M.; Wang, X.; Yang, L.; Li, Z. The CpG Dinucleotide Adjacent to a κB Site Affects NF-κB Function through Its Methylation. Int. J. Mol. Sci. 2017, 18, 528.

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