Principles of dimer-specific gene regulation revealed by a comprehensive characterization of NF-κB family DNA binding

被引:168
作者
Siggers, Trevor [1 ]
Chang, Abraham B. [2 ,3 ]
Teixeira, Ana [4 ]
Wong, Daniel [4 ]
Williams, Kevin J. [2 ,3 ]
Ahmed, Bilal [1 ,5 ]
Ragoussis, Jiannis [4 ]
Udalova, Irina A. [6 ]
Smale, Stephen T. [2 ,3 ]
Bulyk, Martha L. [1 ,5 ,7 ]
机构
[1] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA
[2] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA
[3] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA
[4] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
[5] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol, Boston, MA USA
[6] Univ London Imperial Coll Sci Technol & Med, Kennedy Inst Rheumatol, London, England
[7] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
基金
英国医学研究理事会; 英国惠康基金; 美国国家卫生研究院;
关键词
TRANSCRIPTION-FACTOR-BINDING; ACTIVATION; MICROARRAYS; MOTIFS; CELLS; SEQUENCE; INNATE; SITES; RECOGNITION; MODULATION;
D O I
10.1038/ni.2151
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The unique DNA-binding properties of distinct NF-kappa B dimers influence the selective regulation of NF-kappa B target genes. To more thoroughly investigate these dimer-specific differences, we combined protein-binding microarrays and surface plasmon resonance to evaluate DNA sites recognized by eight different NF-kappa B dimers. We observed three distinct binding-specificity classes and clarified mechanisms by which dimers might regulate distinct sets of genes. We identified many new nontraditional NF-kappa B binding site (kappa B site) sequences and highlight the plasticity of NF-kappa B dimers in recognizing kappa B sites with a single consensus half-site. This study provides a database that can be used in efforts to identify NF-kappa B target sites and uncover gene regulatory circuitry.
引用
收藏
页码:95 / U123
页数:9
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