4.7 Article

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

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NATURE IMMUNOLOGY
卷 13, 期 1, 页码 95-U123

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NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2151

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资金

  1. US National Institutes of Health (NIH) [R01 HG003985]
  2. HFSP [RGY0085/2005-C]
  3. NIH [R01 AI073868, T32 CA009120]
  4. FP7 Collaborative Project [222008]
  5. UK Medical Research Council
  6. Wellcome Trust [075491/Z/04]
  7. i2b2/HST Summer Institute in Bioinformatics and Integrative Genomics NIH [U54 LM008748]
  8. MRC [G0700818] Funding Source: UKRI
  9. Medical Research Council [G0700818] Funding Source: researchfish
  10. NATIONAL CANCER INSTITUTE [T32CA009120] Funding Source: NIH RePORTER
  11. NATIONAL HUMAN GENOME RESEARCH INSTITUTE [R01HG003985] Funding Source: NIH RePORTER
  12. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI073868] Funding Source: NIH RePORTER
  13. NATIONAL LIBRARY OF MEDICINE [U54LM008748] Funding Source: NIH RePORTER

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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.

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