The transcriptional specificity of NF-κB dimers is coded within the κB DNA response elements

Cell Rep. 2012 Oct 25;2(4):824-39. doi: 10.1016/j.celrep.2012.08.042. Epub 2012 Oct 11.

Abstract

Nuclear factor κB (NF-κB) regulates gene expression by binding to specific DNA elements, known collectively as κB sites, that are contained within the promoters/enhancers of target genes. We found that the identity of the central base pair (bp) of κB sites profoundly affects the transcriptional activity of NF-κB dimers. RelA dimers prefer an A/T bp at this position for optimal transcriptional activation (A/T-centric) and discriminate against G/C-centric κB sites. The p52 homodimer, in contrast, activates transcription from G/C-centric κB sites in complex with Bcl3 but represses transcription from the A/T-centric sites. The p52:Bcl3 complex binds to these two classes of κB sites in distinct modes, permitting the recruitment of coactivator, corepressor, or both coactivator and corepressor complexes in promoters that contain G/C-, A/T-, or both G/C- and A/T-centric sites. Therefore, through sensing of bp differences within κB sites, NF-κB dimers modulate biological programs by activating, repressing, and altering the expression of effector genes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Cell Lymphoma 3 Protein
  • Base Sequence
  • Binding Sites
  • Cells, Cultured
  • DNA / metabolism*
  • Dimerization
  • Gene Expression Regulation
  • Kinetics
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • NF-kappa B p52 Subunit / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Proteins / metabolism
  • Response Elements
  • Transcription Factor RelA / metabolism
  • Transcription Factors / metabolism
  • Transcriptional Activation

Substances

  • B-Cell Lymphoma 3 Protein
  • Bcl3 protein, mouse
  • NF-kappa B
  • NF-kappa B p52 Subunit
  • Proto-Oncogene Proteins
  • Transcription Factor RelA
  • Transcription Factors
  • DNA

Associated data

  • GEO/GSE39922