Fig. 8.

Enhancer priming and assisted loading of STAT3 by NF-κB promotes synergistic gene expression. Upon IL-1β treatment, NF-κB binds a subset of ‘assisted enhancers’ (right-hand side), leading to increased p300/CBP-mediated H3K27ac. This event does not lead to prominent gene induction, rather, it primes the enhancer for STAT3 binding which would only be weakly bound without priming (in the IL-6 only treatment). When hepatocytes are exposed to both IL-1β and IL-6 (such as in acute and chronic inflammation), NF-κB assists STAT3 binding, leading to synergistic gene expression. Conversely, the enhancers where most STAT3 sites reside are not primed by NF-κB (‘unassisted sites’, left-hand side) and STAT3 achieves maximal binding in the presence of only IL-6