Figure 1

Regulation of NF-κB by SETD6-mediated methylation of RelA. In resting cells SETD6 binds to and monomethylates chromatin-bound RelA at Lys310 (K310); consequently, the methylation (Me) mark helps recruit ankyrin repeat (ANK)-containing histone methyltransferase GLP, which subsequently methylates histone H3K9 via its SET domain, leading to condensation of local chromatin and repression of NF-κB genes. Upon TNF-α stimulation, PKC-ζ induces phosphorylation (P) of Ser311 (S311), which then prevents the recruitment of GLP, methylation of histone H3K9 and the formation of condensed chromatin. The replacement of the methylated H3K9, likely by acetylation (Ac), allows the expression of NF-κB target genes.