Coordinated binding of NF-κB family members in the response of human cells to lipopolysaccharide
- 11 April 2006
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 103 (15), 5899-5904
- https://doi.org/10.1073/pnas.0510996103
Abstract
The NF-κB family of transcription factors plays a critical role in numerous cellular processes, particularly the immune response. Our understanding of how the different NF-κB 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-κB 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-κB subunits bound to these genes and to other genes. Genes that became bound by multiple NF-κB subunits were the most likely to show increases in RNA polymerase II occupancy and gene expression. This study identifies NF-κB target genes, reveals how the different NF-κB proteins coordinate their activity, and provides an initial map of the transcriptional regulatory network that underlies the host response to infection.Keywords
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