Control of NF-κB-dependent Transcriptional Responses by Chromatin Organization

Abstract

A large number of genes have been positively selected and recruited to participate in various phases of the inflammatory response triggered by microbial stimuli. Because of the complexity of the response, the many phases in which it is deployed, and the many “flavors” in which it appears (depending on quality and intensity of the stimulus as well as the target organ), very elaborated mechanisms evolved to ensure that the expression of the induced genes is carefully and precisely organized so that each gene is expressed in response to specific stimuli and with kinetics and intensities that suit the peculiar function of its product(s). Data accumulated in recent years have strengthened the concept that chromatin is an essential substrate at which multiple signals are integrated to promote a correctly choreographed expression of the genes involved in inflammatory transcriptional responses. Although the current level of understanding of these mechanisms is far from complete, some concepts and ideas have resisted experimental challenges and now represent accepted paradigms that are the subject of this article.