The activated p65 subunit of NF-κB undergoes acetylation in the nucleus at multiple lysine residues including K122, K123, K218, K221 and K310 [23, 111]. The opposing activities of histone acetyltransferases and histone deacetylases (HDACs) regulate p65 complex acetylation [24]. Acetylation of p65 also depends on coactivators such as p300 and CREB-binding protein (CBP) [112]. The K221 and K310 acetylation are associated with increased NF-κB target gene transcription [112] and are required for p65 activation [24], which is supported by the observations that SIRT driven deacetylation at K310 inhibits NF-κB target gene transcription [113]. Additionally, K122 and K123 acetylation reduces p65 DNA binding affinity and increases IκB interaction and nuclear export [111]. Site-specific p300-mediated p65 acetylation thus regulates the specificity of NF-κB- dependent gene expression [111, 114].
