The multifunctional nuclear protein Daxx is involved in apoptosis and development, but a role for Daxx in innate immunity has not been clearly established. In the Journal of Biological Chemistry, Cao et al. find that Daxx has broad and high expression throughout the immune system. Macrophages stimulated with certain agonists of Toll-like receptors (TLRs) upregulate their expression of Daxx mRNA and protein. Knockdown of Daxx in macrophages boosts the production of interleukin 6 (IL-6) but seems to leave other proinflammatory cytokines, such as IL-12 or interferon-β, intact. After macrophages are stimulated, Daxx is mobilized selectively to the proximal promoter of Il6, where it recruits the histone deacetylase HDAC1. Daxx therefore seems to be a selective negative regulator of inflammation that acts through epigenetic modification of the Il6 locus.

J. Biol. Chem. 289, 9372–9379 (2014)