title: The CpG Dinucleotide Adjacent to a κB Site Affects NF-κB Function through Its Methylation.
abstract: 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.
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Science, Jilin University, Changchun 130012, China. wangtaodluf@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Science, Jilin University, Changchun 130012, China. lijg2012772002@163.com.
authors.forename: Jinge
authors.initials: J
authors.lastname: Li
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Science, Jilin University, Changchun 130012, China. m15250953673@163.com.
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Science, Jilin University, Changchun 130012, China. m13844142327@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Science, Jilin University, Changchun 130012, China. 15843056163@163.com.
authors.forename: Qiuru
authors.initials: Q
authors.lastname: Che
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Science, Jilin University, Changchun 130012, China. sunxiuming222@163.com.
authors.forename: Xiuming
authors.initials: X
authors.lastname: Sun
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Science, Jilin University, Changchun 130012, China. daiyumeng_jlu@163.com.
authors.forename: Yumeng
authors.initials: Y
authors.lastname: Dai
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Science, Jilin University, Changchun 130012, China. sunwei1067@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Science, Jilin University, Changchun 130012, China. baomeiying1984@126.com.
authors.forename: Meiying
authors.initials: M
authors.lastname: Bao
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Science, Jilin University, Changchun 130012, China. sirzhe@outlook.com.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Wang
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Science, Jilin University, Changchun 130012, China. yanglq@jlu.edu.cn.
authors.forename: Liquan
authors.initials: L
authors.lastname: Yang
authors.affiliation: The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Science, Jilin University, Changchun 130012, China. zhiweili@jlu.edu.cn.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D016384:Consensus Sequence; D018899:CpG Islands; D019175:DNA Methylation; D005786:Gene Expression Regulation; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D016328:NF-kappa B
keywords: CpG islands; NF-κB; consensus sequence; methylation