Tuning up inflammation: how DNA sequence and chromatin organization control the induction of inflammatory genes by NF-kappaB.

NF-kappaB is a collective name given to a family of ubiquitous transcription factors (TFs) activated in response to inflammatory stimuli and environmental stressors, and required for the activation of many crucial inflammatory and immune response genes. NF-kappaB is activated by degradation of its cytoplasmic anchors, the IkappaBs, and subsequent nuclear translocation and accumulation. Once entered in the nucleus NF-kappaB activates transcription of hundreds of genes; however, each inflammatory gene must be expressed and turned off with peculiar kinetics that suit its specific function. Chromatin organization plays a major role in controlling the kinetics of NF-kappaB recruitment to target genes and it represents an integration point mediating TF cooperativity.