Coordinated binding of NF-kappaB family members in the response of human cells to lipopolysaccharide

Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5899-904. doi: 10.1073/pnas.0510996103. Epub 2006 Apr 4.

Abstract

The NF-kappaB family of transcription factors plays a critical role in numerous cellular processes, particularly the immune response. Our understanding of how the different NF-kappaB subunits act coordinately to regulate gene expression is based on a limited set of genes. We used genome-scale location analysis to identify targets of all five NF-kappaB proteins before and after stimulation of monocytic cells with bacterial lipopolysaccharide (LPS). In unstimulated cells, p50 and p52 bound to a large number of gene promoters that were also occupied by RNA polymerase II. After LPS stimulation, additional NF-kappaB subunits bound to these genes and to other genes. Genes that became bound by multiple NF-kappaB subunits were the most likely to show increases in RNA polymerase II occupancy and gene expression. This study identifies NF-kappaB target genes, reveals how the different NF-kappaB proteins coordinate their activity, and provides an initial map of the transcriptional regulatory network that underlies the host response to infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genome, Human
  • Humans
  • Lipopolysaccharides / pharmacology*
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism*
  • Protein Binding
  • Protein Subunits / metabolism
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • Transcription, Genetic / drug effects
  • U937 Cells

Substances

  • Lipopolysaccharides
  • NF-kappa B
  • Protein Subunits
  • RNA Polymerase II