Genome-wide mapping of RELA(p65) binding identifies E2F1 as a transcriptional activator recruited by NF-kappaB upon TLR4 activation

Mol Cell. 2007 Aug 17;27(4):622-35. doi: 10.1016/j.molcel.2007.06.038.


NF-kappaB is a key mediator of inflammation. Here, we mapped the genome-wide loci bound by the RELA subunit of NF-kappaB in lipopolysaccharide (LPS)-stimulated human monocytic cells, and together with global gene expression profiling, found an overrepresentation of the E2F1-binding motif among RELA-bound loci associated with NF-kappaB target genes. Knockdown of endogenous E2F1 impaired the LPS inducibility of the proinflammatory cytokines CCL3(MIP-1alpha), IL23A(p19), TNF-alpha, and IL1-beta. Upon LPS stimulation, E2F1 is rapidly recruited to the promoters of these genes along with p50/RELA heterodimer via a mechanism that is dependent on NF-kappaB activation. Together with the observation that E2F1 physically interacts with p50/RELA in LPS-stimulated cells, our findings suggest that NF-kappaB recruits E2F1 to fully activate the transcription of NF-kappaB target genes. Global gene expression profiling subsequently revealed a spectrum of NF-kappaB target genes that are positively regulated by E2F1, further demonstrating the critical role of E2F1 in the Toll-like receptor 4 pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Consensus Sequence
  • Cytokines / metabolism
  • E2F1 Transcription Factor / metabolism*
  • Gene Expression Regulation / drug effects
  • Genome, Human / genetics*
  • Humans
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / pharmacology
  • Molecular Sequence Data
  • Protein Binding / drug effects
  • Protein Transport / drug effects
  • Retinoblastoma Protein / metabolism
  • Toll-Like Receptor 4 / metabolism*
  • Trans-Activators / metabolism*
  • Transcription Factor RelA / metabolism*


  • Cytokines
  • E2F1 Transcription Factor
  • Inflammation Mediators
  • Lipopolysaccharides
  • Retinoblastoma Protein
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Trans-Activators
  • Transcription Factor RelA