EGR1 Inhibits Pro-Inflammatory Genes in Macrophages

Scientists at The Wistar Institute discovered that early growth response 1 (EGR1), inhibits expression of pro-inflammatory genes in macrophages. The discovery expands the understanding of how macrophages are set off and deactivated in the inflammatory process, which is critical in many normal and pathological conditions. These findings were published in Science Advances.

"By deepening the understanding of the role of EGR1, we shed light on the fundamental process of macrophage maturation, which is required for many aspects of the immune response including inflammation," said Alessandro Gardini, senior author on the study. "Our data suggest EGR1 acts as a master regulator of inflammation in macrophages."

Gardini and colleagues used a model to recreate differentiation of monocytes to macrophages in vitro and performed a systematic genomic analysis of the role of EGR1 in this process. They found that EGR1 binds to different DNA regulatory regions in late-differentiating macrophages as opposed to progenitor cells differentiating into monocytes.

The team had previously uncovered a mechanism through which EGR1 regulates gene expression in monocytes and macrophages by interacting with enhancers. These are short regulatory DNA sequences that, when bound by specific transcription factors, augment the expression of the associated genes. In the new study, researchers found that EGR1 represses inflammatory enhancers in developing and mature macrophages, blunting their activation and the immune response.

"Our results suggest that the role of EGR1 in modulating inflammation may extend beyond development of blood cells and be relevant to the control of inflammation in health and disease conditions," concluded Avery Zucco, co-first author of the study.