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

The NF-kappa B family of transcription factors plays a critical role in numerous cellular processes, particularly the immune response. Our understanding of how the different NF-kappa B 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-kappa B 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-kappa B subunits bound to these genes and to other genes. Genes that became bound by multiple NF-kappa B subunits were the most likely to show increases in RNA polymerase 11 occupancy and gene expression. This study identifies NF-kappa B target genes, reveals how the different NF-kappa B proteins coordinate their activity, and provides an initial map of the transcriptional regulatory network that underlies the host response to infection.