Specialized Chromatin Patterns in the Control of Inflammatory Gene Expression

Abstract

Inflammatory responses to microbial and non-microbial stimuli involve coordinate changes in the expression of hundreds of genes. The inflammatory gene expression programs display two important features: first, alternative stimuli affect both a large set of common genes and a variable number of stimulus-specific genes. Second, different genes are activated with different kinetics over several hours after the initial stimulus. Mechanistically, these features reflect the interplay between two main groups of determinants: the combinatorial control of transcription by multiple transcription factors, with NF-kappaB and the IRFs playing a central and essential role in the induction of a large fraction of inflammatory genes; and the presence of well-defined, in part cell-type specific, patterns of chromatin organization at cis-regulatory regions of inflammatory genes. Recent advancements in this field are providing paradigms of general value explaining how inducible responses to environmental stimuli are controlled.