Coordinated binding of NF-kappaB family members in the response of human cells to lipopolysaccharide.
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.
Schreiber
Joerg
J
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Jenner
Richard G
RG
Murray
Heather L
HL
Gerber
Georg K
GK
Gifford
David K
DK
Young
Richard A
RA
D015894:Genome, Human; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D020298:U937 Cells
D008070:Lipopolysaccharides; D016328:NF-kappa B; D021122:Protein Subunits; D012319:RNA Polymerase II