Figure 1.

Organization and function of macrophage-specific enhancers responsive to inflammatory stimuli. The essential macrophage fate-determining TF Pu.1 activates as enhancers the genomic regions it binds. Enhancer organization entails both the formation of a nucleosome-free region centered on the Pu.1-binding site and the deposition of histone modifications like H3K4me1. A fraction of the macrophage-specific enhancers contains binding sites for TFs activated by inflammatory stimuli (like NF-kB), which are recruited in response to stimulation. Binding sites for sequence-specific transcriptional repressors (e.g., Bcl-6) are involved in negative regulation of enhancer activity. Bcl-6 association with most genomic regions it binds is attenuated or completely eliminated in response to inflammatory stimuli.