Pharmacological inhibition of bromodomain-containing proteins in inflammation

Abstract

Inflammation is associated with the activation of genes that contribute to immune defense and tissue repair. The bromodomain- containing proteins of the BET family, which recognize histone lysine acetylation, play a key role in the transcriptional control of inflammatory genes. Inhibition of BET proteins by the small-molecule inhibitor I-BET affects the expression of a particular subset of inflammatory genes-namely, ones that follow an "analog-like," but not "digital-like" activation pattern. This ability of I-BET to target genes based on the dynamic pattern of their activation may facilitate the further development of anti-inflammatory treatment protocols that are tuned to the individual or to disease-specific patterns of gene expression. © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.