[Perspective] Unwinding inducible gene expression
The inflammatory response is coordinated by hundreds of genes that promote host defense against infection and injury. Inducible expression of these genes is mediated by distinct mechanisms, including transcriptional elongation, histone modifications, and nucleosome remodeling. On page 1074 of this issue, Rialdi et al. (1) report that a subset of the genes activated by viral infections depends on topoisomerase 1 (Top1) for induced expression. Pharmacological targeting of specific gene subsets has many clinical applications in inflammatory diseases. Because Top1 inhibition primarily affects genes dependent on nucleosome remodeling, many of which are key drivers of inflammation, it holds promise for gene-specific manipulation of the inflammatory response. Authors: Scott D. Pope, Ruslan Medzhitov